Objective:To study the correlation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression with inflammatory response and matrix metalloproteinases (MMPs) /TIMPs in patients with myocardial infarction.M...Objective:To study the correlation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression with inflammatory response and matrix metalloproteinases (MMPs) /TIMPs in patients with myocardial infarction.Methods: The patients who were diagnosed with acute myocardial infarction and the patients who were diagnosed with stable angina pectoris in the Second People's Hospital of Juancheng County between March 2014 and December 2017 were selected as the AMI group and SAP group respectively, and the healthy volunteers who received physical examination during the same period were selected as the control group. Peripheral blood was collected to detect the expression of EMMPRIN, and serum was collected to determine the contents of inflammatory cytokines and MMPs/TIMPs. Results: Peripheral blood EMMPRIN expression as well as serum ICAM1, VCAM1, IL-1β, IL-17, MMP2, MMP8 and MMP9 contents of AMI group and SAP group were significantly higher than those of control group whereas TGF-β1, sFGL-2, TIMP1 and TIMP2 contents were significantly lower than those of control group and the changes of above indexes in AMI group were more significant than those in SAP group. Serum ICAM1, VCAM1, IL-1β, IL-17, MMP2, MMP8 and MMP9 contents of AMI group of patients with high EMMPRIN expression were significantly higher than those of patients with low EMMPRIN expression whereas TGF-β1, sFGL-2, TIMP1 and TIMP2 contents were significantly lower than those of patients with low EMMPRIN expression.Conclusion:The high EMMPRIN expression in peripheral blood of patients with myocardial infarction can aggravate the inflammatory response and destroy the balance of MMPs/TIMPs.展开更多
Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sect...Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.展开更多
The matrix metalloproteinase (MMP) stromelysin-3 (ST3) has long been implicated to play an important role in extracellular matrix (ECM) remodeling and cell fate determination during normal and pathological processes. ...The matrix metalloproteinase (MMP) stromelysin-3 (ST3) has long been implicated to play an important role in extracellular matrix (ECM) remodeling and cell fate determination during normal and pathological processes. However like other MMPs, the molecular basis of ST3 function in vivo remains unclear due to the lack of information on its physiological substrates. Furthermore, ST3 has only weak activities toward all tested ECM proteins. Using thyroid hormone-dependent Xenopus laevis metamorphosis as a model, we demonstrated previously that ST3 is important for apoptosis and tissue morphogenesis during intestinal remodeling. Here, we used yeast two-hybrid screen with mRNAs from metamorphosing tadpoles to identify potential substrate of ST3 during development. We thus isolated the 37 kd laminin receptor precursor (LR). We showed that LR binds to ST3 in vitro and can be cleaved by ST3 at two sites distinct from where other MMPs cleave. Through peptide sequencing, we determined that the two cleavage sites are in the extracellular domain between the transmembrane domain and laminin binding sequence. Furthermore, we demon strated that these cleavage sites are conserved in human LR. These results together with high levels of human LR and ST3 expression in carcinomas suggest that LR is a likely in vivo substrate of ST3 and that its cleavage by ST3 may alter cell-extracellular matrix interaction, thus, playing a role in mediating the effects of ST3 on cell fate and behavior ob- served during development and pathogenesis.展开更多
INTRODUCTIONLiver fibrosis is an excessive deposition ofextracellular matrix(ECM)resulted from bothincreased synthesis and decreased degradation.Matrix metalloproteinases(MMPs)represent agroup of neutral proteinases w...INTRODUCTIONLiver fibrosis is an excessive deposition ofextracellular matrix(ECM)resulted from bothincreased synthesis and decreased degradation.Matrix metalloproteinases(MMPs)represent agroup of neutral proteinases with variable展开更多
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP) play a significant role in regulating angiogenesis, the process of new blood vessel formation. Interstitial collagenase (MMP-1), 72 k...Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP) play a significant role in regulating angiogenesis, the process of new blood vessel formation. Interstitial collagenase (MMP-1), 72 kDa gelatinase A/type IV collagenase (MMP-2), and 92 kDa gelatinase B/type IV collagenase (MMP-9) dissolve extracellular matrix (ECM) and may initiate and Promote angiogenesis. TIMP-1, TIMP-2, TIMP-3, and possibly,TIMP-4 inhibit neovascularisation. A new paradigm is emerging that matrilysin (MMP-7), MMP-9, and metalloelastase (MMP-12) may block angiogehesis by converting plasndnogen to angiostatin, which is one of the most potent angiogenesis antagonists. MMPs and TIMPs play a complex role in regulating angiogenesis. An understanding of the biochemical and cellular pathways and mechanisms of angiogenesis will provide importal information to allow the control of angiogenesis, e.g. the stimulation of angiogenesis for coronary collateral circulation formation; while the inhibition for treating arthritis and cancer.展开更多
Objective: Procyanidins (PC) are widely available natural polyphenols. The present study is designed to investigate if PC can inhibit angiogenesis in lung adenocarcinoma xenografts through crosslinking vascular extrac...Objective: Procyanidins (PC) are widely available natural polyphenols. The present study is designed to investigate if PC can inhibit angiogenesis in lung adenocarcinoma xenografts through crosslinking vascular extracellular matrix (ECM) and preventing proteolysis by matrix metalloproteinases (MMPs). Methods: Using the in vitro MMP-2 proteolysis and in vivo subcutaneous implantation models, we investigated if PC crosslinking inhibits MMP-mediated proteolysis. Using a cultured cell detachment assay, an in vitro angiogenesis assay, and a cell proliferation assay, we investigated if PC inhibits MMP-2-mediated endothelial cell detachment, angiogenesis, and cell proliferation, respectively. Using tumor xenografts, we evaluated if PC can inhibit growth of lung adenocarcinoma. Results: PC crosslink vascular ECM proteins, protecting them against proteolysis by MMPs in vitro and in vivo, protecting cultured human umbilical vein endothelial cells from detachment by MMP-2, and inhibiting in vitro angiogenesis. However, PC (0.75-100 μg/mL) did not inhibit vascular and tumor cells proliferation. PC injections (30 mg PC/kg bodyweight) in situ had anticancer effects on xenografts of lung adenocarcinoma, most likely by inhibiting angiogenesis during ECM proteolysis by MMPs. Conclusion: The results suggest that PC may be important MMP inhibitors that can be used as therapeutic anticancer agents.展开更多
Karacoline is a compound found in the plant Aconitum kusnezoffii Reichb.Although Aconitum kusnezoffii Reichb is widely used for the treatment of pain,very few studies have been carried out on the use of karacoline due...Karacoline is a compound found in the plant Aconitum kusnezoffii Reichb.Although Aconitum kusnezoffii Reichb is widely used for the treatment of pain,very few studies have been carried out on the use of karacoline due to its potential toxicity.In this study,we selected key matrix metalloproteinases(MMPs),collagen II,and aggrecan as targets due to their association with intervertebral disc degeneration(IDD).Using these targets,we then used network pharmacology to predict a series of molecules that might exert therapeutic effects on IDD.Of these molecules,karacoline was predicted to have the best effect.Tumor necrosis factor(TNF)-a is known to promote the degeneration of the extracellular matrix in IDD.We therefore applied different concentrations of karacoline(0,1.25,or 12.88 mM)along with 100 ng/mL TNF-a to rat nucleus pulposus cells and found that karacoline reduced the expression of MMP-14 in IDD by inhibiting the nuclear factor(NF)-κB pathway,while collagen II and aggrecan expression was increased.This suggested that extracellular matrix degradation was inhibited by karacoline(P<0.05).Our data therefore reveal a new clinical application of karacoline and provide support for the use of network pharmacology in predicting novel drugs.展开更多
BACKGROUND Bariatric surgery is an efficient strategy for body weight and type 2 diabetes mellitus(T2 DM) management. Abnormal lipid deposition in visceral organs,especially the pancreas and liver, might cause beta-ce...BACKGROUND Bariatric surgery is an efficient strategy for body weight and type 2 diabetes mellitus(T2 DM) management. Abnormal lipid deposition in visceral organs,especially the pancreas and liver, might cause beta-cell dysfunction and insulin resistance. Extracellular matrix(ECM) remodeling allows adipose expansion, and matrix metalloproteinases(MMPs) play essential roles in ECM construction.MMP-2 and MMP-9 are the substrates of MMP-7. Different studies have reported that MMP-2,-7, and-9 increase in patients with obesity and metabolic syndromes or T2 DM and are considered biomarkers in obesity and hyperglycemia patients.AIMTo prospectively investigate whether MMP-2, MMP-7, and MMP-9 differ after two bariatric surgeries: Gastric bypass(GB) and sleeve gastrectomy(SG).METHODS We performed GB in 23 and SG in 19 obese patients with T2 DM. We measured body weight, waist circumference, body mass index(BMI), and serum concentrations of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood sugar(FBS),hemoglobin A1 c(Hb A1 c), C-peptide, homeostasis model assessments of insulin resistance, and MMP-2, MMP-7, and MMP-9 levels at baseline and at 3, 12, and 24 mo post-operation.RESULTS Twenty-three patients aged 44.7 ± 9.7 years underwent GB, and 19 patients aged40.1 ± 9.1 years underwent SG. In the GB group, BMI decreased from 30.3 ± 3.4 to24.4 ± 2.4 kg/m2, Hb A1 c decreased from 9.2% ± 1.5% to 6.7% ± 1.4%, and FBS decreased from 171.6 ± 65.0 mg/d L to 117.7 ± 37.5 mg/d L 2 years post-operation(P < 0.001). However, the MMP-2, MMP-7, and MMP-9 levels pre-and post-GB were similar even 2 years post-operation(P = 0.107, 0.258, and 0.466,respectively). The SG group revealed similar results: BMI decreased from 36.2 ±5.1 to 26.9 ± 4.7 kg/m2, Hb A1 c decreased from 7.9% ± 1.7% to 5.8% ± 0.6%, and FBS decreased from 138.3 ± 55.6 mg/d L to 95.1 ± 3.1 mg/d L(P < 0.001). The serum MMP-2,-7, and-9 levels pre-and post-SG were not different(P = 0.083,0.869, and 0.1, respectively).CONCLUSION Improvements in obesity and T2 DM induced by bariatric surgery might be the result of MMP-2,-7, or-9 independent pathways.展开更多
AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury.METHODS: Gastric ulcers were generated in rats by ...AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury.METHODS: Gastric ulcers were generated in rats by administration of 70% ethanol,and activity of doxycycline was tested by administration 30 min prior to ethanol.Similarly,the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model.The activities and expression of MMPs were examined by zymography and Western blot analysis.RESULTS: Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen,either indomethacin or ethanol,was reversed significantly by doxycycline.Indomethacin-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control tissues.Similarly,ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities,respectively,in rat gastric tissues.Both proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric tissues.In contrast,the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer prevention.On the other hand,doxycycline inhibited significantly proMMP-9,-2 and -3 activities in vitro.In addition,doxycycline reduced oxidative load in gastric tissues and scavenged H2O2 in vitro.Our results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ulcers.CONCLUSION: This is the first demonstration of dual action of doxycycline,that is,regulation of MMP activity and reduction of oxidative stress in arresting gastric injury.展开更多
The main pathophysiology of cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Resveratrol has been reported to be one of the most potent chemop...The main pathophysiology of cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Resveratrol has been reported to be one of the most potent chemopreventive agents that can inhibit cellular processes associated with ischemic stroke. Matrix metalloproteinases(MMPs) has been considered as a potential drug target for the treatment of cerebral ischemia. To explore this, we tried to investigate the interaction of resveratrol with MMPs through molecular docking studies. At 30 minutes before and 2 hours after cerebral ischemia/reperfusion induced by occlusion of the middle cerebral artery, 40 mg/kg resveratrol was intraperitoneally administered. After resveratrol administration, neurological function and brain edema were significantly alleviated, cerebral infarct volume was significantly reduced, and nitrite and malondialdehyde levels in the cortical and striatal regions were significantly decreased. The molecular docking study of resveratrol and MMPs revealed that resveratrol occupied the active site of MMP-2 and MMP-9. The binding energy of the complexes was –37.848672 k J/mol and –36.6345 k J/mol for MMP-2 and MMP-9, respectively. In case of MMP-2, Leu 164, Ala 165 and Thr 227 were engaged in H-Bonding with resveratrol and in case of MMP-9, H-bonding was found with Glu 402, Ala 417 and Arg 424 residues. These findings collectively reveal that resveratrol exhibits neuroprotective effects on cerebral ischemia through inhibiting MMP-2 and MMP-9 activity.展开更多
The matrix metalloproteinases(MMPs) are a family of zinc-dependent endopeptidases originally characterized as secreted proteases responsible for degrading extracellular matrix proteins.Their canonical role in matrix r...The matrix metalloproteinases(MMPs) are a family of zinc-dependent endopeptidases originally characterized as secreted proteases responsible for degrading extracellular matrix proteins.Their canonical role in matrix remodelling is of significant importance in neural development and regeneration,but emerging roles for MMPs,especially in signal transduction pathways,are also of obvious importance in a neural context.Misregulation of MMP activity is a hallmark of many neuropathologies,and members of every branch of the MMP family have been implicated in aspects of neural development and disease.However,while extraordinary research efforts have been made to elucidate the molecular mechanisms involving MMPs,methodological constraints and complexities of the research models have impeded progress.Here we discuss the current state of our understanding of the roles of MMPs in neural development using recent examples and advocate a phylogenetically diverse approach to MMP research as a means to both circumvent the challenges associated with specific model organisms,and to provide a broader evolutionary context from which to synthesize an understanding of the underlying biology.展开更多
BACKGROUND Matrix metalloproteinases(MMPs)participate in the degradation of extracellular matrix compounds,maintaining the homeostasis between fibrogenesis and fibrolytic processes in the liver.However,there are few s...BACKGROUND Matrix metalloproteinases(MMPs)participate in the degradation of extracellular matrix compounds,maintaining the homeostasis between fibrogenesis and fibrolytic processes in the liver.However,there are few studies on the regulation of liver MMPs in fibrosis progression in humans.AIM To assess the production activity and regulation of matrix metalloproteinases in liver fibrosis stages in chronic hepatitis C(CHC).METHODS A prospective,cross-sectional,multicenter study was conducted.CHC patients were categorized in fibrosis grades through FibroTest®and/or FibroScan®.Serum MMP-2,-7,and-9 were determined by western blot and multiplex suspension array assays.Differences were validated by the Kruskal-Wallis and Mann-Whitney U tests.The Spearman correlation coefficient and area under the receiver operating characteristic curve were calculated.Collagenolytic and gelatinase activity was determined through the Azocoll substrate and zymogram test,whereas tissue inhibitor of metalloproteinase-1 production was determined by dot blot assays.RESULTS Serum concentrations of the MMPs evaluated were higher in CHC patients than in healthy subjects.MMP-7 distinguished early and advanced stages,with a correlation of 0.32(P<0.001),and the area under the receiver operating characteristic displayed moderate sensitivity and specificity for MMP-7 in F4(area under the receiver operating characteristic,0.705;95%confidence interval:0.605-0.805;P<0.001).Collagenolytic activity was detected at F0 and F1,whereas gelatinase activity was not detected at any fibrosis stage.Tissue inhibitor of metalloproteinase-1 determination showed upregulation in F0 and F1 but downregulation in F2(P<0.001).CONCLUSION High concentrations of inactive MMPs were present in the serum of CHC patients,reflecting the impossibility to restrain liver fibrosis progression.MMPs could be good diagnostic candidates and therapeutic targets for improving novel strategies to reverse liver fibrosis in CHC.展开更多
Objective:To study the effects of phentolamine on myocardial extracellular matrix of cardiac remodeling induced by norepinephrine in rats.Methods:24 SD rats were divided into 3 groups randomly:control groups,norepinep...Objective:To study the effects of phentolamine on myocardial extracellular matrix of cardiac remodeling induced by norepinephrine in rats.Methods:24 SD rats were divided into 3 groups randomly:control groups,norepinephrine groups(model groups),norepinephrine +phentolamine groups(treatment groups).Echocardiography was used to detect changes in cardiac structure and function,the level of collagen volume fraction(CVF) and hydroxy-proline as well as collagen content were determined in myocardial tissue,matrix metalloproteinases-2 and collagen Ⅰin myocardial tissue were localized by immunohistochemitry.Results:Compared with control groups,left ventricular hypertrophy in the model group rats,the livdioxyproline content and CVF was significantly higher(P<0.01),and matrix metalloproteinase- 2 and collagen Ⅰ protein expression was significantly increased(P<0.01).Phentolamine significantly improved cardiac hypertrophy in treatment group rats,reduced hydroxy-proline,CVF,matrix metalloproteinase 2and collagen Ⅰ protein expression(P<0.05).Conclusions:Phentolamine can effectively reduce the incidence of myocardial hypertrophy and myocardial extracellular matrix remodeling in SD rats,and it can ease myocardial extracellular matrix of cardiac remodeling.It may he associated with reduced expression of matrix metalloproteinase 2 and collagen Ⅰ in myocardial tissue remodeling.展开更多
AIM To study activation of extracellular signal-regulated kinase-1/2(ERK1/2) and pro-matrix metalloproteinases(pro-MMPs) secretion from isolated primary human ciliary muscle(h-CM) cells in response to bradykinin(BK) a...AIM To study activation of extracellular signal-regulated kinase-1/2(ERK1/2) and pro-matrix metalloproteinases(pro-MMPs) secretion from isolated primary human ciliary muscle(h-CM) cells in response to bradykinin(BK) and other agonists. METHODS Serum-starved h-CM cells were challenged with vehicle, BK agonists or antagonists. Cell lysates were evaluated for phosphorylated ERK1/2 using homogeneous timeresolved fluorescence technology based on a sandwich immunoassay. Rabbit polyclonal anti-pro-MMP antibodies were used to measure pro-MMPs using immunoblot analysis.RESULTS A 10 min incubation time using 5 × 104 h-CM cells/well was optimum condition for studying stimulation of ERK1/2 phosphorylation. BK(100 nmol/L) caused a 1.86 ± 0.26 fold(n = 3) increase in ERK1/2 phosphorylation above baseline. BK analogs, Met-Lys-BK and RMP-7(100 nmol/L), also stimulated ERK1/2 phosphorylation by 1.57 ± 0.04 and 1.55 ± 0.09 fold, respectively. However, DesArg9-Bradykinin, a B1 receptor-selective agonist(0.1-1 μmol/L), was essentially inactive. HOE-140 or WIN-64338(B2-antagonists) appreciably blocked phosphorylation of ERK1/2 induced by various BK agonists. Pre-treatmentof cells with a prostaglandin(PG) synthase inhibitor(bromfenac; 1 μmol/L) failed to alter kinin-induced ERK1/2 activation. BK and a non-peptide BK agonist(FR-190997)(10 nmol/L-1 μmol/L) also enhanced pro-MMPs secretion(pro-MMP-1 > pro-MMP-3 > pro-MMP-2; 1.45-1.75-fold over baseline) from h-CM cells. CONCLUSION These collective data suggest that B2 kinin receptors initiate signaling in h-CM cells by a relatively rapid mechanism(within minutes) involving ERK1/2 activation which in turn regulates MMPs production(within hours). The latter process does not involve PGs.展开更多
Objective: The aim of this study was to investigate the effects of probe puncture on the expression of VEGF, PLA2 and PGE2 and extracellular matrix collagen and metabolic enzymes in the intervertebral disc of rats wit...Objective: The aim of this study was to investigate the effects of probe puncture on the expression of VEGF, PLA2 and PGE2 and extracellular matrix collagen and metabolic enzymes in the intervertebral disc of rats with cervical disc degeneration. Methods: Rats were randomly assigned to the following three groups (n = 25 per group): sham operation group (cut neck and then suture), model group (treated by modeling), and acupuncture treatment group (continuous daily) 30 minutes, complete course of treatment consisted of 14 days, 2 days between two courses);mRNA expression levels of VEGF, PLA2 and PGE2 were analyzed by qRT-PCR;protein levels of VEGF, PLA2 and PGE2 proteins were determined by Western blotting;Immunohistochemical staining was used to detect type I and type II collagen;TNF-α, IL-1β, MMP-1 and MMP-3 levels were detected by enzyme-linked immunosorbent assay;TUNEL assay was used to evaluate acupuncture treatment for cervical disc degeneration The effect of apoptosis. Results: The expression levels of VEGF, PLA2 and PGE2 mRNA and protein in the model group were higher than those in the sham operation group, while the acupuncture treatment group reduced the expression levels of VEGF, PLA2 and PGE2 mRNA and protein in the model group (P<0.05). The type I collagen was positively correlated with disc degeneration, and type II collagen was negatively correlated with disc degeneration. In the model group (0.18±0.05, 0.11±0.03), the expression level of type I collagen was higher than that of the sham operation group (0.12±0.03), the expression level of type II collagen was decreased (0.19±0.04), and the acupuncture treatment group was able to restore the model. Collagen levels of group I (0.14±0.03) and type II (0.17±0.03) were different between the three groups (P<0.05). Compared with the sham operation group, the model group was TNF-α, IL-1β, The expression levels of MMP-1 and MMP-3 were increased, while the acupuncture treatment group reduced the expression levels of TNF-α, IL-1β, MMP-1 and MMP-3 in the model group (P<0.05). The nuclear membrane of the model group was destroyed, the nucleus became denser, and the cells in the acupuncture treatment group showed a relatively intact nuclear membrane. The number of TUNEL-positive cells in the model group (131.17±12.15) was increased compared with the sham-operated group (64.53±8.73). Compared with the model group, the number of TUNEL-positive cells in the acupuncture treatment group decreased (P<0.05). Conclusion: Acupuncture can reduce the expression of type I collagen and metabolic enzymes in VEGF, PLA2 and PGE2 and extracellular matrix of cervical intervertebral disc degeneration, and increase the expression of type II collagen.展开更多
Objective: To study the relationship of MMPs/TIMPs expression and extracellular matrix component levels in uterosacral ligament with apoptosis in patients with stress urinary incontinence (SUI). Methods: A total of 48...Objective: To study the relationship of MMPs/TIMPs expression and extracellular matrix component levels in uterosacral ligament with apoptosis in patients with stress urinary incontinence (SUI). Methods: A total of 48 patients who were diagnosed with stress urinary incontinence and received surgical treatment in Zigong First People's Hospital between May 2011 and October 2016 were selected as SUI group, and 30 patients who received vaginal hysterectomy for benign tumor during the same period were selected as control group. The uterosacral ligament was collected during operation to determine the mRNA expression of MMPs/TIMPs and apoptosis genes as well as the levels of extracellular matrix components. Results: MMP1, MMP2, MMP9, MMP14, Bax, Caspase-3, Caspase-9 and LC3-II mRNA expression in uterosacral ligament of SUI group were significantly higher than those of control group while TIMP1, TIMP2 and TIMP3 mRNA expression as well as Col-I, Col-III, Elastin, PYD and Fibulin-5 levels were significantly lower than those of control group;Bax, Caspase-3, Caspase-9 and LC3-II mRNA expression in uterosacral ligament were positively correlated with MMP1, MMP2, MMP9 and MMP14 mRNA expression, and negatively correlated with TIMP1, TIMP2 and TIMP3 mRNA expression as well as Col-I, Col-III, Elastin, PYD and Fibulin-5 levels. Conclusion: The excessive apoptosis in uterosacral ligament of patients with stress urinary incontinence is related to the imbalance of MMPs/TIMPs and the excessive degradation of extracellular matrix components.展开更多
文摘Objective:To study the correlation of extracellular matrix metalloproteinase inducer (EMMPRIN) expression with inflammatory response and matrix metalloproteinases (MMPs) /TIMPs in patients with myocardial infarction.Methods: The patients who were diagnosed with acute myocardial infarction and the patients who were diagnosed with stable angina pectoris in the Second People's Hospital of Juancheng County between March 2014 and December 2017 were selected as the AMI group and SAP group respectively, and the healthy volunteers who received physical examination during the same period were selected as the control group. Peripheral blood was collected to detect the expression of EMMPRIN, and serum was collected to determine the contents of inflammatory cytokines and MMPs/TIMPs. Results: Peripheral blood EMMPRIN expression as well as serum ICAM1, VCAM1, IL-1β, IL-17, MMP2, MMP8 and MMP9 contents of AMI group and SAP group were significantly higher than those of control group whereas TGF-β1, sFGL-2, TIMP1 and TIMP2 contents were significantly lower than those of control group and the changes of above indexes in AMI group were more significant than those in SAP group. Serum ICAM1, VCAM1, IL-1β, IL-17, MMP2, MMP8 and MMP9 contents of AMI group of patients with high EMMPRIN expression were significantly higher than those of patients with low EMMPRIN expression whereas TGF-β1, sFGL-2, TIMP1 and TIMP2 contents were significantly lower than those of patients with low EMMPRIN expression.Conclusion:The high EMMPRIN expression in peripheral blood of patients with myocardial infarction can aggravate the inflammatory response and destroy the balance of MMPs/TIMPs.
基金supported by the Construction of Prevention and Treatment System of Geriatric Syndromes Focusing on Disability and Dementia(No.21-1-2-2-zyyd-nsh)。
文摘Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were collected.Fourteen SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic regression.The multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)modeling.Results Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 rs1053605.Carriers of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased risk.CCL2 rs4586 and MMP-2 rs14070 exhibited the most significant interactions.Conclusion CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.
文摘The matrix metalloproteinase (MMP) stromelysin-3 (ST3) has long been implicated to play an important role in extracellular matrix (ECM) remodeling and cell fate determination during normal and pathological processes. However like other MMPs, the molecular basis of ST3 function in vivo remains unclear due to the lack of information on its physiological substrates. Furthermore, ST3 has only weak activities toward all tested ECM proteins. Using thyroid hormone-dependent Xenopus laevis metamorphosis as a model, we demonstrated previously that ST3 is important for apoptosis and tissue morphogenesis during intestinal remodeling. Here, we used yeast two-hybrid screen with mRNAs from metamorphosing tadpoles to identify potential substrate of ST3 during development. We thus isolated the 37 kd laminin receptor precursor (LR). We showed that LR binds to ST3 in vitro and can be cleaved by ST3 at two sites distinct from where other MMPs cleave. Through peptide sequencing, we determined that the two cleavage sites are in the extracellular domain between the transmembrane domain and laminin binding sequence. Furthermore, we demon strated that these cleavage sites are conserved in human LR. These results together with high levels of human LR and ST3 expression in carcinomas suggest that LR is a likely in vivo substrate of ST3 and that its cleavage by ST3 may alter cell-extracellular matrix interaction, thus, playing a role in mediating the effects of ST3 on cell fate and behavior ob- served during development and pathogenesis.
基金Natural Science Foundation of Committee of Science and Technology of Shanghai Municipality(952B14003)Science and Technology Development Foundation of Educational Committee of Shanghai Municipality(96B06).
文摘INTRODUCTIONLiver fibrosis is an excessive deposition ofextracellular matrix(ECM)resulted from bothincreased synthesis and decreased degradation.Matrix metalloproteinases(MMPs)represent agroup of neutral proteinases with variable
文摘Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP) play a significant role in regulating angiogenesis, the process of new blood vessel formation. Interstitial collagenase (MMP-1), 72 kDa gelatinase A/type IV collagenase (MMP-2), and 92 kDa gelatinase B/type IV collagenase (MMP-9) dissolve extracellular matrix (ECM) and may initiate and Promote angiogenesis. TIMP-1, TIMP-2, TIMP-3, and possibly,TIMP-4 inhibit neovascularisation. A new paradigm is emerging that matrilysin (MMP-7), MMP-9, and metalloelastase (MMP-12) may block angiogehesis by converting plasndnogen to angiostatin, which is one of the most potent angiogenesis antagonists. MMPs and TIMPs play a complex role in regulating angiogenesis. An understanding of the biochemical and cellular pathways and mechanisms of angiogenesis will provide importal information to allow the control of angiogenesis, e.g. the stimulation of angiogenesis for coronary collateral circulation formation; while the inhibition for treating arthritis and cancer.
基金supported by National "863" High-tech R & D Program of China(No. 2007AA03Z317)the National Natural Science Foundation of China(No.31070870)+1 种基金"973" Program of the Ministry of Science and Technology of China (No.2007CB714502, 2007CB936000)Shanghai Municipal Committee of Science and Techology (No. 08520740300, 1052nm06100 and 09JC1416500)
文摘Objective: Procyanidins (PC) are widely available natural polyphenols. The present study is designed to investigate if PC can inhibit angiogenesis in lung adenocarcinoma xenografts through crosslinking vascular extracellular matrix (ECM) and preventing proteolysis by matrix metalloproteinases (MMPs). Methods: Using the in vitro MMP-2 proteolysis and in vivo subcutaneous implantation models, we investigated if PC crosslinking inhibits MMP-mediated proteolysis. Using a cultured cell detachment assay, an in vitro angiogenesis assay, and a cell proliferation assay, we investigated if PC inhibits MMP-2-mediated endothelial cell detachment, angiogenesis, and cell proliferation, respectively. Using tumor xenografts, we evaluated if PC can inhibit growth of lung adenocarcinoma. Results: PC crosslink vascular ECM proteins, protecting them against proteolysis by MMPs in vitro and in vivo, protecting cultured human umbilical vein endothelial cells from detachment by MMP-2, and inhibiting in vitro angiogenesis. However, PC (0.75-100 μg/mL) did not inhibit vascular and tumor cells proliferation. PC injections (30 mg PC/kg bodyweight) in situ had anticancer effects on xenografts of lung adenocarcinoma, most likely by inhibiting angiogenesis during ECM proteolysis by MMPs. Conclusion: The results suggest that PC may be important MMP inhibitors that can be used as therapeutic anticancer agents.
文摘Karacoline is a compound found in the plant Aconitum kusnezoffii Reichb.Although Aconitum kusnezoffii Reichb is widely used for the treatment of pain,very few studies have been carried out on the use of karacoline due to its potential toxicity.In this study,we selected key matrix metalloproteinases(MMPs),collagen II,and aggrecan as targets due to their association with intervertebral disc degeneration(IDD).Using these targets,we then used network pharmacology to predict a series of molecules that might exert therapeutic effects on IDD.Of these molecules,karacoline was predicted to have the best effect.Tumor necrosis factor(TNF)-a is known to promote the degeneration of the extracellular matrix in IDD.We therefore applied different concentrations of karacoline(0,1.25,or 12.88 mM)along with 100 ng/mL TNF-a to rat nucleus pulposus cells and found that karacoline reduced the expression of MMP-14 in IDD by inhibiting the nuclear factor(NF)-κB pathway,while collagen II and aggrecan expression was increased.This suggested that extracellular matrix degradation was inhibited by karacoline(P<0.05).Our data therefore reveal a new clinical application of karacoline and provide support for the use of network pharmacology in predicting novel drugs.
基金Supported by grants from MinSheng General Hospital,Taoyuan,Far Eastern Memorial Hospital-National Yang-Ming University Joint Research Program,No. 105DN15,No. 106DN15,and No. 107DN14 to Lee TH and Chen CY。
文摘BACKGROUND Bariatric surgery is an efficient strategy for body weight and type 2 diabetes mellitus(T2 DM) management. Abnormal lipid deposition in visceral organs,especially the pancreas and liver, might cause beta-cell dysfunction and insulin resistance. Extracellular matrix(ECM) remodeling allows adipose expansion, and matrix metalloproteinases(MMPs) play essential roles in ECM construction.MMP-2 and MMP-9 are the substrates of MMP-7. Different studies have reported that MMP-2,-7, and-9 increase in patients with obesity and metabolic syndromes or T2 DM and are considered biomarkers in obesity and hyperglycemia patients.AIMTo prospectively investigate whether MMP-2, MMP-7, and MMP-9 differ after two bariatric surgeries: Gastric bypass(GB) and sleeve gastrectomy(SG).METHODS We performed GB in 23 and SG in 19 obese patients with T2 DM. We measured body weight, waist circumference, body mass index(BMI), and serum concentrations of total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, fasting blood sugar(FBS),hemoglobin A1 c(Hb A1 c), C-peptide, homeostasis model assessments of insulin resistance, and MMP-2, MMP-7, and MMP-9 levels at baseline and at 3, 12, and 24 mo post-operation.RESULTS Twenty-three patients aged 44.7 ± 9.7 years underwent GB, and 19 patients aged40.1 ± 9.1 years underwent SG. In the GB group, BMI decreased from 30.3 ± 3.4 to24.4 ± 2.4 kg/m2, Hb A1 c decreased from 9.2% ± 1.5% to 6.7% ± 1.4%, and FBS decreased from 171.6 ± 65.0 mg/d L to 117.7 ± 37.5 mg/d L 2 years post-operation(P < 0.001). However, the MMP-2, MMP-7, and MMP-9 levels pre-and post-GB were similar even 2 years post-operation(P = 0.107, 0.258, and 0.466,respectively). The SG group revealed similar results: BMI decreased from 36.2 ±5.1 to 26.9 ± 4.7 kg/m2, Hb A1 c decreased from 7.9% ± 1.7% to 5.8% ± 0.6%, and FBS decreased from 138.3 ± 55.6 mg/d L to 95.1 ± 3.1 mg/d L(P < 0.001). The serum MMP-2,-7, and-9 levels pre-and post-SG were not different(P = 0.083,0.869, and 0.1, respectively).CONCLUSION Improvements in obesity and T2 DM induced by bariatric surgery might be the result of MMP-2,-7, or-9 independent pathways.
基金Supported by Research Fellowship from Council of Scientific and Industrial Research,New Delhi,No.NBA2007 of DBT,IAP001 and CLP 261 of NTRF
文摘AIM: To examine the effect of doxycycline on the activity of matrix metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats following gastric injury.METHODS: Gastric ulcers were generated in rats by administration of 70% ethanol,and activity of doxycycline was tested by administration 30 min prior to ethanol.Similarly,the effect of doxycycline was tested in an indomethacin-induced gastric ulcer model.The activities and expression of MMPs were examined by zymography and Western blot analysis.RESULTS: Gastric injury in rats as judged by elevated ulcer indices following exposure to ulcerogen,either indomethacin or ethanol,was reversed significantly by doxycycline.Indomethacin-induced ulcerated gastric tissues exhibited about 12-fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as compared to control tissues.Similarly,ethanol induced about 22-fold and about 6-fold higher proMMP-9 and proMMP-3 activities,respectively,in rat gastric tissues.Both proMMP-9 and MMP-3 activities were markedly decreased by doxycycline in ulcerogen treated rat gastric tissues.In contrast,the reduced MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer prevention.On the other hand,doxycycline inhibited significantly proMMP-9,-2 and -3 activities in vitro.In addition,doxycycline reduced oxidative load in gastric tissues and scavenged H2O2 in vitro.Our results suggest a novel regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action on MMP-9 and MMP-3 during prevention of gastric ulcers.CONCLUSION: This is the first demonstration of dual action of doxycycline,that is,regulation of MMP activity and reduction of oxidative stress in arresting gastric injury.
文摘The main pathophysiology of cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Resveratrol has been reported to be one of the most potent chemopreventive agents that can inhibit cellular processes associated with ischemic stroke. Matrix metalloproteinases(MMPs) has been considered as a potential drug target for the treatment of cerebral ischemia. To explore this, we tried to investigate the interaction of resveratrol with MMPs through molecular docking studies. At 30 minutes before and 2 hours after cerebral ischemia/reperfusion induced by occlusion of the middle cerebral artery, 40 mg/kg resveratrol was intraperitoneally administered. After resveratrol administration, neurological function and brain edema were significantly alleviated, cerebral infarct volume was significantly reduced, and nitrite and malondialdehyde levels in the cortical and striatal regions were significantly decreased. The molecular docking study of resveratrol and MMPs revealed that resveratrol occupied the active site of MMP-2 and MMP-9. The binding energy of the complexes was –37.848672 k J/mol and –36.6345 k J/mol for MMP-2 and MMP-9, respectively. In case of MMP-2, Leu 164, Ala 165 and Thr 227 were engaged in H-Bonding with resveratrol and in case of MMP-9, H-bonding was found with Glu 402, Ala 417 and Arg 424 residues. These findings collectively reveal that resveratrol exhibits neuroprotective effects on cerebral ischemia through inhibiting MMP-2 and MMP-9 activity.
文摘The matrix metalloproteinases(MMPs) are a family of zinc-dependent endopeptidases originally characterized as secreted proteases responsible for degrading extracellular matrix proteins.Their canonical role in matrix remodelling is of significant importance in neural development and regeneration,but emerging roles for MMPs,especially in signal transduction pathways,are also of obvious importance in a neural context.Misregulation of MMP activity is a hallmark of many neuropathologies,and members of every branch of the MMP family have been implicated in aspects of neural development and disease.However,while extraordinary research efforts have been made to elucidate the molecular mechanisms involving MMPs,methodological constraints and complexities of the research models have impeded progress.Here we discuss the current state of our understanding of the roles of MMPs in neural development using recent examples and advocate a phylogenetically diverse approach to MMP research as a means to both circumvent the challenges associated with specific model organisms,and to provide a broader evolutionary context from which to synthesize an understanding of the underlying biology.
基金the National Council for Science and Technology,No.SALUD-2016-272579 and No.PAPIIT-UNAM TA200515.
文摘BACKGROUND Matrix metalloproteinases(MMPs)participate in the degradation of extracellular matrix compounds,maintaining the homeostasis between fibrogenesis and fibrolytic processes in the liver.However,there are few studies on the regulation of liver MMPs in fibrosis progression in humans.AIM To assess the production activity and regulation of matrix metalloproteinases in liver fibrosis stages in chronic hepatitis C(CHC).METHODS A prospective,cross-sectional,multicenter study was conducted.CHC patients were categorized in fibrosis grades through FibroTest®and/or FibroScan®.Serum MMP-2,-7,and-9 were determined by western blot and multiplex suspension array assays.Differences were validated by the Kruskal-Wallis and Mann-Whitney U tests.The Spearman correlation coefficient and area under the receiver operating characteristic curve were calculated.Collagenolytic and gelatinase activity was determined through the Azocoll substrate and zymogram test,whereas tissue inhibitor of metalloproteinase-1 production was determined by dot blot assays.RESULTS Serum concentrations of the MMPs evaluated were higher in CHC patients than in healthy subjects.MMP-7 distinguished early and advanced stages,with a correlation of 0.32(P<0.001),and the area under the receiver operating characteristic displayed moderate sensitivity and specificity for MMP-7 in F4(area under the receiver operating characteristic,0.705;95%confidence interval:0.605-0.805;P<0.001).Collagenolytic activity was detected at F0 and F1,whereas gelatinase activity was not detected at any fibrosis stage.Tissue inhibitor of metalloproteinase-1 determination showed upregulation in F0 and F1 but downregulation in F2(P<0.001).CONCLUSION High concentrations of inactive MMPs were present in the serum of CHC patients,reflecting the impossibility to restrain liver fibrosis progression.MMPs could be good diagnostic candidates and therapeutic targets for improving novel strategies to reverse liver fibrosis in CHC.
基金supported by Jiangsu Province Natural Science Foundationof China:v2716298
文摘Objective:To study the effects of phentolamine on myocardial extracellular matrix of cardiac remodeling induced by norepinephrine in rats.Methods:24 SD rats were divided into 3 groups randomly:control groups,norepinephrine groups(model groups),norepinephrine +phentolamine groups(treatment groups).Echocardiography was used to detect changes in cardiac structure and function,the level of collagen volume fraction(CVF) and hydroxy-proline as well as collagen content were determined in myocardial tissue,matrix metalloproteinases-2 and collagen Ⅰin myocardial tissue were localized by immunohistochemitry.Results:Compared with control groups,left ventricular hypertrophy in the model group rats,the livdioxyproline content and CVF was significantly higher(P<0.01),and matrix metalloproteinase- 2 and collagen Ⅰ protein expression was significantly increased(P<0.01).Phentolamine significantly improved cardiac hypertrophy in treatment group rats,reduced hydroxy-proline,CVF,matrix metalloproteinase 2and collagen Ⅰ protein expression(P<0.05).Conclusions:Phentolamine can effectively reduce the incidence of myocardial hypertrophy and myocardial extracellular matrix remodeling in SD rats,and it can ease myocardial extracellular matrix of cardiac remodeling.It may he associated with reduced expression of matrix metalloproteinase 2 and collagen Ⅰ in myocardial tissue remodeling.
文摘AIM To study activation of extracellular signal-regulated kinase-1/2(ERK1/2) and pro-matrix metalloproteinases(pro-MMPs) secretion from isolated primary human ciliary muscle(h-CM) cells in response to bradykinin(BK) and other agonists. METHODS Serum-starved h-CM cells were challenged with vehicle, BK agonists or antagonists. Cell lysates were evaluated for phosphorylated ERK1/2 using homogeneous timeresolved fluorescence technology based on a sandwich immunoassay. Rabbit polyclonal anti-pro-MMP antibodies were used to measure pro-MMPs using immunoblot analysis.RESULTS A 10 min incubation time using 5 × 104 h-CM cells/well was optimum condition for studying stimulation of ERK1/2 phosphorylation. BK(100 nmol/L) caused a 1.86 ± 0.26 fold(n = 3) increase in ERK1/2 phosphorylation above baseline. BK analogs, Met-Lys-BK and RMP-7(100 nmol/L), also stimulated ERK1/2 phosphorylation by 1.57 ± 0.04 and 1.55 ± 0.09 fold, respectively. However, DesArg9-Bradykinin, a B1 receptor-selective agonist(0.1-1 μmol/L), was essentially inactive. HOE-140 or WIN-64338(B2-antagonists) appreciably blocked phosphorylation of ERK1/2 induced by various BK agonists. Pre-treatmentof cells with a prostaglandin(PG) synthase inhibitor(bromfenac; 1 μmol/L) failed to alter kinin-induced ERK1/2 activation. BK and a non-peptide BK agonist(FR-190997)(10 nmol/L-1 μmol/L) also enhanced pro-MMPs secretion(pro-MMP-1 > pro-MMP-3 > pro-MMP-2; 1.45-1.75-fold over baseline) from h-CM cells. CONCLUSION These collective data suggest that B2 kinin receptors initiate signaling in h-CM cells by a relatively rapid mechanism(within minutes) involving ERK1/2 activation which in turn regulates MMPs production(within hours). The latter process does not involve PGs.
文摘Objective: The aim of this study was to investigate the effects of probe puncture on the expression of VEGF, PLA2 and PGE2 and extracellular matrix collagen and metabolic enzymes in the intervertebral disc of rats with cervical disc degeneration. Methods: Rats were randomly assigned to the following three groups (n = 25 per group): sham operation group (cut neck and then suture), model group (treated by modeling), and acupuncture treatment group (continuous daily) 30 minutes, complete course of treatment consisted of 14 days, 2 days between two courses);mRNA expression levels of VEGF, PLA2 and PGE2 were analyzed by qRT-PCR;protein levels of VEGF, PLA2 and PGE2 proteins were determined by Western blotting;Immunohistochemical staining was used to detect type I and type II collagen;TNF-α, IL-1β, MMP-1 and MMP-3 levels were detected by enzyme-linked immunosorbent assay;TUNEL assay was used to evaluate acupuncture treatment for cervical disc degeneration The effect of apoptosis. Results: The expression levels of VEGF, PLA2 and PGE2 mRNA and protein in the model group were higher than those in the sham operation group, while the acupuncture treatment group reduced the expression levels of VEGF, PLA2 and PGE2 mRNA and protein in the model group (P<0.05). The type I collagen was positively correlated with disc degeneration, and type II collagen was negatively correlated with disc degeneration. In the model group (0.18±0.05, 0.11±0.03), the expression level of type I collagen was higher than that of the sham operation group (0.12±0.03), the expression level of type II collagen was decreased (0.19±0.04), and the acupuncture treatment group was able to restore the model. Collagen levels of group I (0.14±0.03) and type II (0.17±0.03) were different between the three groups (P<0.05). Compared with the sham operation group, the model group was TNF-α, IL-1β, The expression levels of MMP-1 and MMP-3 were increased, while the acupuncture treatment group reduced the expression levels of TNF-α, IL-1β, MMP-1 and MMP-3 in the model group (P<0.05). The nuclear membrane of the model group was destroyed, the nucleus became denser, and the cells in the acupuncture treatment group showed a relatively intact nuclear membrane. The number of TUNEL-positive cells in the model group (131.17±12.15) was increased compared with the sham-operated group (64.53±8.73). Compared with the model group, the number of TUNEL-positive cells in the acupuncture treatment group decreased (P<0.05). Conclusion: Acupuncture can reduce the expression of type I collagen and metabolic enzymes in VEGF, PLA2 and PGE2 and extracellular matrix of cervical intervertebral disc degeneration, and increase the expression of type II collagen.
文摘Objective: To study the relationship of MMPs/TIMPs expression and extracellular matrix component levels in uterosacral ligament with apoptosis in patients with stress urinary incontinence (SUI). Methods: A total of 48 patients who were diagnosed with stress urinary incontinence and received surgical treatment in Zigong First People's Hospital between May 2011 and October 2016 were selected as SUI group, and 30 patients who received vaginal hysterectomy for benign tumor during the same period were selected as control group. The uterosacral ligament was collected during operation to determine the mRNA expression of MMPs/TIMPs and apoptosis genes as well as the levels of extracellular matrix components. Results: MMP1, MMP2, MMP9, MMP14, Bax, Caspase-3, Caspase-9 and LC3-II mRNA expression in uterosacral ligament of SUI group were significantly higher than those of control group while TIMP1, TIMP2 and TIMP3 mRNA expression as well as Col-I, Col-III, Elastin, PYD and Fibulin-5 levels were significantly lower than those of control group;Bax, Caspase-3, Caspase-9 and LC3-II mRNA expression in uterosacral ligament were positively correlated with MMP1, MMP2, MMP9 and MMP14 mRNA expression, and negatively correlated with TIMP1, TIMP2 and TIMP3 mRNA expression as well as Col-I, Col-III, Elastin, PYD and Fibulin-5 levels. Conclusion: The excessive apoptosis in uterosacral ligament of patients with stress urinary incontinence is related to the imbalance of MMPs/TIMPs and the excessive degradation of extracellular matrix components.
