The proliferation of glomerular mesangial cells (GMC) and secretion of the extracellular matrix (ECM) in rat with Thy-1 nephritis (Thy-1N) resembling human mesangioproliferative glomerulonephritis have been explored f...The proliferation of glomerular mesangial cells (GMC) and secretion of the extracellular matrix (ECM) in rat with Thy-1 nephritis (Thy-1N) resembling human mesangioproliferative glomerulonephritis have been explored for many years; however, the molecular mechanisms of GMC proliferation and ECM production remain unclear. Our previous studies have demonstrated that the thrombospondin-1 (TSP-1) gene was involved in mediating rat GMC proliferation and ECM synthesis induced by sublytic C5b-9 in vitro. In the present study, the roles of the TSP-1 gene in GMC proliferation, ECM production, and urinary protein secretion in Thy-1N rats were determined by using TSP-1 small hairpin RNA, and the results revealed that silencing of the TSP-1 gene in rat renal tissues could diminish GMC proliferation (P < 0.01) and ECM secretion (P < 0.01) as well as urinary protein secretion (P < 0.05) in Thy-1N rats. Together, the current findings suggested that TSP-1 gene expression was required for GMC proliferation and ECM production in Thy-1N rats.展开更多
Freezing tolerance is a significant trait in plants that grow in cold environments and survive through the winter.Apple(Malus domestica Borkh.)is a cold-tolerant fruit tree,and the cold tolerance of its bark is import...Freezing tolerance is a significant trait in plants that grow in cold environments and survive through the winter.Apple(Malus domestica Borkh.)is a cold-tolerant fruit tree,and the cold tolerance of its bark is important for its survival at low temperatures.However,little is known about the gene activity related to its freezing tolerance.To better understand the gene expression and regulation properties of freezing tolerance in dormant apple trees,we analyzed the transcriptomic divergences in the bark from 1-year-old branches of two apple cultivars,“Golden Delicious”(G)and“Jinhong”(H),which have different levels of cold resistance,under chilling and freezing treatments.“H”can safely overwinter below−30℃in extremely low-temperature regions,whereas“G”experiences severe freezing damage and death in similar environments.Based on 28 bark transcriptomes(from the epidermis,phloem,and cambium)from 1-year-old branches under seven temperature treatments(from 4 to−29°C),we identified 4173 and 7734 differentially expressed genes(DEGs)in“G”and“H”,respectively,between the chilling and freezing treatments.A gene coexpression network was constructed according to this expression information using weighted gene correlation network analysis(WGCNA),and seven biologically meaningful coexpression modules were identified from the network.The expression profiles of the genes from these modules suggested the gene regulatory pathways that are responsible for the chilling and freezing stress responses of“G”and/or“H.”Module 7 was probably related to freezing acclimation and freezing damage in“H”at the lower temperatures.This module contained more interconnected hub transcription factors(TFs)and cold-responsive genes(CORs).Modules 6 and 7 contained C-repeat binding factor(CBF)TFs,and many CBF-dependent homologs were identified as hub genes.We also found that some hub TFs had higher intramodular connectivity(KME)and gene significance(GS)than CBFs.Specifically,most hub TFs in modules 6 and 7 were activated at the beginning of the early freezing stress phase and maintained upregulated expression during the whole freezing stress period in“G”and“H”.The upregulation of DEGs related to methionine and carbohydrate biosynthetic processes in“H”under more severe freezing stress supported the maintenance of homeostasis in the cellular membrane.This study improves our understanding of the transcriptional regulation patterns underlying freezing tolerance in the bark of apple branches.展开更多
The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)inductio...The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.展开更多
Interleukin 17(IL-17)is increasingly recognized as a key factor that contributes to the pathogenesis of multiple sclerosis(MS)and its experimental mouse autoimmune encephalomyelitis(EAE)model.However,the roles and reg...Interleukin 17(IL-17)is increasingly recognized as a key factor that contributes to the pathogenesis of multiple sclerosis(MS)and its experimental mouse autoimmune encephalomyelitis(EAE)model.However,the roles and regulatory mechanisms of IL-17-induced pro-inflammatory cytokine production in EAE mice remain largely unclear.In this study,the expression of IL-17,hypoxia inducible factor-1α(HIF-1α),IL-1β,IL-6 and microRNA-497(miR-497),as well as their intrinsic associations,was investigated using EAE model mice and cultured astrocytes exposed to IL-17 in vitro.We observed markedly increased production of IL-17,HIF-1α,IL-1βand IL-6 in the brain tissues of EAE mice,while the expression and secretion of HIF-1α,IL-1βand IL-6 were also significantly increased when cultured primary astrocytes from mice were stimulated with IL-17.Meanwhile,the expression of miR-497 was downregulated both in vivo and in vitro.Subsequent in vitro experiments revealed that IL-17 induced the production of IL-1βand IL-6 in astrocytes through the upregulation of HIF-1αas a transcriptional factor,indicating that IL-17-mediated downregulation of miR-497 enhanced HIF-1αexpression.Furthermore,astrocytespecific knockdown of IL-17RA and HIF-1αor astrocyte-specific overexpression of miR-497 by infection with different lentiviral vectors containing an astrocyte-specific promotor markedly decreased IL-1βand IL-6 production in brain tissues and alleviated the pathological changes and score of EAE mice.Collectively,these findings indicate that decreased miR-497 expression is responsible for IL-17-triggered high HIF-1αexpression and consequent IL-1βand IL-6 production by astrocytes in EAE mice.展开更多
基金supported by grants from National Natural Science Foundations of China (No. 31000396, and No.81072402)grants from Natural Science Foundations of Jiangsu Province in China (No. BK2009417, No. 10KJB310006, and No. 09hx43)
文摘The proliferation of glomerular mesangial cells (GMC) and secretion of the extracellular matrix (ECM) in rat with Thy-1 nephritis (Thy-1N) resembling human mesangioproliferative glomerulonephritis have been explored for many years; however, the molecular mechanisms of GMC proliferation and ECM production remain unclear. Our previous studies have demonstrated that the thrombospondin-1 (TSP-1) gene was involved in mediating rat GMC proliferation and ECM synthesis induced by sublytic C5b-9 in vitro. In the present study, the roles of the TSP-1 gene in GMC proliferation, ECM production, and urinary protein secretion in Thy-1N rats were determined by using TSP-1 small hairpin RNA, and the results revealed that silencing of the TSP-1 gene in rat renal tissues could diminish GMC proliferation (P < 0.01) and ECM secretion (P < 0.01) as well as urinary protein secretion (P < 0.05) in Thy-1N rats. Together, the current findings suggested that TSP-1 gene expression was required for GMC proliferation and ECM production in Thy-1N rats.
基金supported by the Agricultural Science and Technology Innovation Program of Jilin Province,“Precise identification and QTL location of cold resistance of new apple germplasm”(program number,CXGC2017JQ020)“Phylogenetic reconstruction technique and gene family reconstruction technique of Malus plants”(program number,C8223001602).
文摘Freezing tolerance is a significant trait in plants that grow in cold environments and survive through the winter.Apple(Malus domestica Borkh.)is a cold-tolerant fruit tree,and the cold tolerance of its bark is important for its survival at low temperatures.However,little is known about the gene activity related to its freezing tolerance.To better understand the gene expression and regulation properties of freezing tolerance in dormant apple trees,we analyzed the transcriptomic divergences in the bark from 1-year-old branches of two apple cultivars,“Golden Delicious”(G)and“Jinhong”(H),which have different levels of cold resistance,under chilling and freezing treatments.“H”can safely overwinter below−30℃in extremely low-temperature regions,whereas“G”experiences severe freezing damage and death in similar environments.Based on 28 bark transcriptomes(from the epidermis,phloem,and cambium)from 1-year-old branches under seven temperature treatments(from 4 to−29°C),we identified 4173 and 7734 differentially expressed genes(DEGs)in“G”and“H”,respectively,between the chilling and freezing treatments.A gene coexpression network was constructed according to this expression information using weighted gene correlation network analysis(WGCNA),and seven biologically meaningful coexpression modules were identified from the network.The expression profiles of the genes from these modules suggested the gene regulatory pathways that are responsible for the chilling and freezing stress responses of“G”and/or“H.”Module 7 was probably related to freezing acclimation and freezing damage in“H”at the lower temperatures.This module contained more interconnected hub transcription factors(TFs)and cold-responsive genes(CORs).Modules 6 and 7 contained C-repeat binding factor(CBF)TFs,and many CBF-dependent homologs were identified as hub genes.We also found that some hub TFs had higher intramodular connectivity(KME)and gene significance(GS)than CBFs.Specifically,most hub TFs in modules 6 and 7 were activated at the beginning of the early freezing stress phase and maintained upregulated expression during the whole freezing stress period in“G”and“H”.The upregulation of DEGs related to methionine and carbohydrate biosynthetic processes in“H”under more severe freezing stress supported the maintenance of homeostasis in the cellular membrane.This study improves our understanding of the transcriptional regulation patterns underlying freezing tolerance in the bark of apple branches.
基金National Natural Science Foundation of China(Grants Numbers 81902878 and 81971468).
文摘The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains unclear.In the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and invasion.Mechanism investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to IL-17.Meanwhile,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and invasion.Besides,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all alleviated.Collectively,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.
基金by the grants from National Natural Science Foundations of China(31470853 and 81471626)grants from Natural Science Foundations of Jiangsu Province in China(BK20131386 and BK20151168)+1 种基金The study was also supported by grants from Jiangsu Province Key Lab of Neurodegeneration(No.SJ11KF07)the Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,Excellent Young or Middle aged Teachers Project of Nanjing Medical University and Xuzhou Technology Bureau Foundation(KC14SH074).
文摘Interleukin 17(IL-17)is increasingly recognized as a key factor that contributes to the pathogenesis of multiple sclerosis(MS)and its experimental mouse autoimmune encephalomyelitis(EAE)model.However,the roles and regulatory mechanisms of IL-17-induced pro-inflammatory cytokine production in EAE mice remain largely unclear.In this study,the expression of IL-17,hypoxia inducible factor-1α(HIF-1α),IL-1β,IL-6 and microRNA-497(miR-497),as well as their intrinsic associations,was investigated using EAE model mice and cultured astrocytes exposed to IL-17 in vitro.We observed markedly increased production of IL-17,HIF-1α,IL-1βand IL-6 in the brain tissues of EAE mice,while the expression and secretion of HIF-1α,IL-1βand IL-6 were also significantly increased when cultured primary astrocytes from mice were stimulated with IL-17.Meanwhile,the expression of miR-497 was downregulated both in vivo and in vitro.Subsequent in vitro experiments revealed that IL-17 induced the production of IL-1βand IL-6 in astrocytes through the upregulation of HIF-1αas a transcriptional factor,indicating that IL-17-mediated downregulation of miR-497 enhanced HIF-1αexpression.Furthermore,astrocytespecific knockdown of IL-17RA and HIF-1αor astrocyte-specific overexpression of miR-497 by infection with different lentiviral vectors containing an astrocyte-specific promotor markedly decreased IL-1βand IL-6 production in brain tissues and alleviated the pathological changes and score of EAE mice.Collectively,these findings indicate that decreased miR-497 expression is responsible for IL-17-triggered high HIF-1αexpression and consequent IL-1βand IL-6 production by astrocytes in EAE mice.
