To investigate the expression of osteopontin （OPN） and its receptor integrin αvβ3 in the placental tissue from pregnant women complicated with preeclampsia, the expression of OPN and αvβ3 in the placenta of the ...To investigate the expression of osteopontin （OPN） and its receptor integrin αvβ3 in the placental tissue from pregnant women complicated with preeclampsia, the expression of OPN and αvβ3 in the placenta of the pregnant women with preeclampsia and healthy pregnant women was detected by immunohistochemistry, Western blotting and RT-PCR. Our results showed that OPN and αvβ3 protein were expressed in the placenta from normal pregnant woman and those with preeclampsia. OPN was located in the placental syncytiotrophoblasts and the cytoplasm of capillary endothelial cells and integrin αvβ3 was mainly expressed on the surface of trophoblast cells. Expression of OPN and integrin αvβ3 in the placental tissue from preeclampsia subjects was significantly lower than that from the control group （P〈0.05）. Compared with the control group, expression of OPN in the placental tissue from preeclampsia group was significantly lower （P〈0.05） but there was no significant difference in the expression of αv and β3 between the preeclampsia group and the controls. It is concluded that OPN and its receptor integrin αvβ3 may be involved in the pathogenesis of preeclampsia.展开更多
Summary： Integrins such as αvβ3, α5β31 play a key role in angiogenesis regulation, invasion and metastasis, inflammation, wound healing, etc. The up-regulation of integrin αvβ3 after cerebral ischemic stroke ca...Summary： Integrins such as αvβ3, α5β31 play a key role in angiogenesis regulation, invasion and metastasis, inflammation, wound healing, etc. The up-regulation of integrin αvβ3 after cerebral ischemic stroke can promote angiogenesis, which in turn improves functional recovery. In addition, the integrin αvβ3 inhibitor can block the blood-brain barrier （BBB） leakage induced by vascular endothelial growth factor （VEGF） and also can reduce inflammatory reaction, decrease the deposition of fibrinogen. Other studies showed that integrin αvβ3 is not essential in revascularization. Therefore, the effect of integrin αvβ3 in the whole process of brain function recovery merits further study.展开更多
Objective: To study the effect of lentivirus-mediated integrin αVβ3-sh RNA on tumor growth of mice with lung cancer xenograft. Methods: Lung cancer tissue, paracancer tissue and normal tissue were collected and inte...Objective: To study the effect of lentivirus-mediated integrin αVβ3-sh RNA on tumor growth of mice with lung cancer xenograft. Methods: Lung cancer tissue, paracancer tissue and normal tissue were collected and integrin αVβ3 expression was detected; BALB/c nude mice were selected, divided into integrin αVβ3 knockdown group(KD group) and negative control group(NC group), and inoculated with cells stably infected by integrin αVβ3-sh RNA lentivirus and cells stably infected by negative control-sh RNA lentivirus respectively, the growth of tumor tissue was continuously observed, and the number of apoptosis cells as well as the expression of angiogenesis, apoptosis and invasion genes in tumor tissue were detected. Results: m RNA content and protein content of integrin αVβ3 in lung cancer tissue were significantly higher than those in paracancer tissue and normal tissue; increasing trend of tumor tissue volume of KD group was weaker than that of NC group, and tumor volume at various points in time of KD group was lower than that of NC group; m RNA contents and protein contents of VEGF, FGF, EGF, Bcl-2, MMP-9, MMP-12 and MMP-13 in tumor tissue of KD group were lower than those of NC group, and apoptosis index as well as m RNA content and protein content of Bax were higher than those of NC group. Conclusions: The expression of integrin αVβ3 increases in lung cancer tissue, and lentivirus-mediated integrin αVβ3-sh RNA can inhibit tumor growth of mice with lung cancer xenografts.展开更多
Objective:To observe the expression of endometrial homologous box gene A10(HOXA10),Integrinαvβ3 and leukemia suppressor factor(LIF)in peri-implantation mice,and to investigate the effect of controlled superovulation...Objective:To observe the expression of endometrial homologous box gene A10(HOXA10),Integrinαvβ3 and leukemia suppressor factor(LIF)in peri-implantation mice,and to investigate the effect of controlled superovulation(COH)on endometrial receptivity in mice.Methods:After COH model preparation and blastocyst transplantation,kunming pure-bred mature mice were randomly divided into natural blastocyst+natural pseudocyst group,COH blastocyst+natural pseudocyst group,natural blastocyst+COH pseudocyst group,and COH blastocyst+COH pseudocyst group.The pregnancy rate and average number of beds in each group were observed on day 6 of conception.Western blot and RT-PCR were used to detect the expression of HOXA10,Integrinααvβ3,LIF protein and mRNA in the endometria of mice on day 5 of conception.Results:The pregnancy rate and average number of beds in the COH group were lower than those in the natural receptor group.The expression of HOXA10,Integrinααvβ3 and LIF in endometrium was significantly lower than that of the natural receptor mice(P<0.01).Conclusion:Superovulation drugs down-regulate the expression of HOXA10,Integrinαvβ3 and LIF in endometrium during the implantation window,reduce endometrial receptivity,and lead to low clinical pregnancy rate.展开更多
BACKGROUND Non-invasive methods to diagnose non-alcoholic steatohepatitis(NASH),an inflammatory subtype of non-alcoholic fatty liver disease(NAFLD),are currently unavailable.AIM To develop an integrinαvβ3-targeted m...BACKGROUND Non-invasive methods to diagnose non-alcoholic steatohepatitis(NASH),an inflammatory subtype of non-alcoholic fatty liver disease(NAFLD),are currently unavailable.AIM To develop an integrinαvβ3-targeted molecular imaging modality to differentiate NASH.METHODS Integrinαvβ3 expression was assessed in Human LO2 hepatocytes Scultured with palmitic and oleic acids(FFA).Hepatic integrinαvβ3 expression was analyzed in rabbits fed a high-fat diet(HFD)and in rats fed a high-fat,high-carbohydrate diet(HFCD).After synthesis,cyclic arginine-glycine-aspartic acid peptide(cRGD)was labeled with gadolinium(Gd)and used as a contrast agent in magnetic resonance imaging(MRI)performed on mice fed with HFCD.RESULTS Integrinαvβ3 was markedly expressed on FFA-cultured hepatocytes,unlike the control hepatocytes.Hepatic integrinαvβ3 expression significantly increased in both HFD-fed rabbits and HFCD-fed rats as simple fatty liver(FL)progressed to steatohepatitis.The distribution of integrinαvβ3 in the liver of NASH cases largely overlapped with albumin-positive staining areas.In comparison to mice with simple FL,the relative liver MRI-T1 signal value at 60 minutes post-injection of Gd-labeled cRGD was significantly increased in mice with steatohepatitis(P<0.05),showing a positive correlation with the NAFLD activity score(r=0.945;P<0.01).Hepatic integrinαvβ3 expression was significantly upregulated during NASH development,with hepatocytes being the primary cells expressing integrinαvβ3.CONCLUSION After using Gd-labeled cRGD as a tracer,NASH was successfully distinguished by visualizing hepatic integrinαvβ3 expression with MRI.展开更多
Previous studies of integrin αvβ3 have focused on ischemic brain damage, although the role of integrin αvβ3 in ischemic preconditioning （IP） has rarely been reported. The present study analyzed the effects of IP...Previous studies of integrin αvβ3 have focused on ischemic brain damage, although the role of integrin αvβ3 in ischemic preconditioning （IP） has rarely been reported. The present study analyzed the effects of IP on integrin αvβ3 mRNA expression following cerebral ischemia through the use of hematoxylin-eosin staining and real-time quantitative polymerase chain reaction techniques. Integrin avid3 mRNA expression in the ischemia group peaked at 24 hours after ischemia-reperfusion. In the IP ＋ ischemia group, integrin αvβ3 mRNA expression increased after 24 hours, but remained significantly less than the ischemia group, and expression continued to increase until 7 days after ischemiaJreperfusion. These results demonstrate that IP effectively attenuated upregulation of integrin αvβ3 mRNA expression at 24 hours after ischemia.展开更多
目的:探讨罗汉果皂苷V(MV)对铁死亡诱导剂RAS选择性致死分子3(RSL3)诱导的人神经母细胞瘤SH-SY5Y细胞铁死亡的抑制作用及可能机制。方法:用RSL3诱导SH-SY5Y细胞建立铁死亡模型。MTT法检测细胞活力;倒置显微镜观察细胞形态;亚铁离子荧光...目的:探讨罗汉果皂苷V(MV)对铁死亡诱导剂RAS选择性致死分子3(RSL3)诱导的人神经母细胞瘤SH-SY5Y细胞铁死亡的抑制作用及可能机制。方法:用RSL3诱导SH-SY5Y细胞建立铁死亡模型。MTT法检测细胞活力;倒置显微镜观察细胞形态;亚铁离子荧光探针FerroFarRed检测细胞内亚铁离子含量;线粒体红色荧光探针MitoTracker Red CMXRos检测线粒体膜电位(MMP);超氧化物阴离子荧光探针二氢乙啶和线粒体超氧化物红色荧光探针MitoSoX Red分别检测细胞内和线粒体内活性氧(ROS)。微板法检测细胞谷胱甘肽(GSH)和丙二醛(MDA)水平。Western blot检测脂酰辅酶A合成酶长链家族成员4(ACSL4)、环加氧酶2(COX-2、)谷胱甘肽过氧化物酶4(GPX4)和溶质载体家族7成员11(SLC7A11)蛋白表达水平。分子对接技术预测MV与ACSL4、COX-2、GPX4和SLC7A11的靶向关系。结果:与control组相比,RSL3组SH-SY5Y细胞活力显著降低(P<0.01),细胞内亚铁离子含量、细胞内和线粒体内ROS水平及MDA水平显著升高(P<0.05或P<0.01),MMP和GSH水平显著降低(P<0.01),ACSL4和COX-2蛋白表达水平显著升高,而GPX4和SLC7A11蛋白表达水平显著降低(P<0.01),提示成功建立了细胞铁死亡模型。MV处理使细胞活力显著升高(P<0.05),细胞内亚铁离子含量、细胞内和线粒体内ROS水平及MDA水平显著降低(P<0.01),MMP和GSH水平显著升高(P<0.05或P<0.01);ACSL4和COX-2蛋白水平显著降低,而GPX4和SLC7A11蛋白水平显著升高(P<0.05或P<0.01)。分子对接结果显示,MV与铁死亡核心蛋白ACSL4、COX-2、GPX4和SLC7A11存在结合位点。结论:MV可抑制RSL3诱导的SH-SY5Y细胞铁死亡的发生,其机制可能与激活SLC7A11/GPX4和抑制ACSL4/COX-2有关。展开更多
基金supported by a grant from Shenzhen Municipal Science and Technology Program (No 200802107)a grant for medical research programs from the Health Department of Guangdong Province (No A2009593)
文摘To investigate the expression of osteopontin （OPN） and its receptor integrin αvβ3 in the placental tissue from pregnant women complicated with preeclampsia, the expression of OPN and αvβ3 in the placenta of the pregnant women with preeclampsia and healthy pregnant women was detected by immunohistochemistry, Western blotting and RT-PCR. Our results showed that OPN and αvβ3 protein were expressed in the placenta from normal pregnant woman and those with preeclampsia. OPN was located in the placental syncytiotrophoblasts and the cytoplasm of capillary endothelial cells and integrin αvβ3 was mainly expressed on the surface of trophoblast cells. Expression of OPN and integrin αvβ3 in the placental tissue from preeclampsia subjects was significantly lower than that from the control group （P〈0.05）. Compared with the control group, expression of OPN in the placental tissue from preeclampsia group was significantly lower （P〈0.05） but there was no significant difference in the expression of αv and β3 between the preeclampsia group and the controls. It is concluded that OPN and its receptor integrin αvβ3 may be involved in the pathogenesis of preeclampsia.
文摘Summary： Integrins such as αvβ3, α5β31 play a key role in angiogenesis regulation, invasion and metastasis, inflammation, wound healing, etc. The up-regulation of integrin αvβ3 after cerebral ischemic stroke can promote angiogenesis, which in turn improves functional recovery. In addition, the integrin αvβ3 inhibitor can block the blood-brain barrier （BBB） leakage induced by vascular endothelial growth factor （VEGF） and also can reduce inflammatory reaction, decrease the deposition of fibrinogen. Other studies showed that integrin αvβ3 is not essential in revascularization. Therefore, the effect of integrin αvβ3 in the whole process of brain function recovery merits further study.
基金supported by Surface Project of National Natural Science Foundation of China(No 81573026)
文摘Objective: To study the effect of lentivirus-mediated integrin αVβ3-sh RNA on tumor growth of mice with lung cancer xenograft. Methods: Lung cancer tissue, paracancer tissue and normal tissue were collected and integrin αVβ3 expression was detected; BALB/c nude mice were selected, divided into integrin αVβ3 knockdown group(KD group) and negative control group(NC group), and inoculated with cells stably infected by integrin αVβ3-sh RNA lentivirus and cells stably infected by negative control-sh RNA lentivirus respectively, the growth of tumor tissue was continuously observed, and the number of apoptosis cells as well as the expression of angiogenesis, apoptosis and invasion genes in tumor tissue were detected. Results: m RNA content and protein content of integrin αVβ3 in lung cancer tissue were significantly higher than those in paracancer tissue and normal tissue; increasing trend of tumor tissue volume of KD group was weaker than that of NC group, and tumor volume at various points in time of KD group was lower than that of NC group; m RNA contents and protein contents of VEGF, FGF, EGF, Bcl-2, MMP-9, MMP-12 and MMP-13 in tumor tissue of KD group were lower than those of NC group, and apoptosis index as well as m RNA content and protein content of Bax were higher than those of NC group. Conclusions: The expression of integrin αVβ3 increases in lung cancer tissue, and lentivirus-mediated integrin αVβ3-sh RNA can inhibit tumor growth of mice with lung cancer xenografts.
基金General program of national natural science foundation of China(No.81674060)Promotion project for special subjects of Jianghan University(No.03100041)。
文摘Objective:To observe the expression of endometrial homologous box gene A10(HOXA10),Integrinαvβ3 and leukemia suppressor factor(LIF)in peri-implantation mice,and to investigate the effect of controlled superovulation(COH)on endometrial receptivity in mice.Methods:After COH model preparation and blastocyst transplantation,kunming pure-bred mature mice were randomly divided into natural blastocyst+natural pseudocyst group,COH blastocyst+natural pseudocyst group,natural blastocyst+COH pseudocyst group,and COH blastocyst+COH pseudocyst group.The pregnancy rate and average number of beds in each group were observed on day 6 of conception.Western blot and RT-PCR were used to detect the expression of HOXA10,Integrinααvβ3,LIF protein and mRNA in the endometria of mice on day 5 of conception.Results:The pregnancy rate and average number of beds in the COH group were lower than those in the natural receptor group.The expression of HOXA10,Integrinααvβ3 and LIF in endometrium was significantly lower than that of the natural receptor mice(P<0.01).Conclusion:Superovulation drugs down-regulate the expression of HOXA10,Integrinαvβ3 and LIF in endometrium during the implantation window,reduce endometrial receptivity,and lead to low clinical pregnancy rate.
基金Supported by the National Natural Science Foundation of China,No.81670513and Young Scientists Fund of the National Natural Science Foundation of China,No.81900511。
文摘BACKGROUND Non-invasive methods to diagnose non-alcoholic steatohepatitis(NASH),an inflammatory subtype of non-alcoholic fatty liver disease(NAFLD),are currently unavailable.AIM To develop an integrinαvβ3-targeted molecular imaging modality to differentiate NASH.METHODS Integrinαvβ3 expression was assessed in Human LO2 hepatocytes Scultured with palmitic and oleic acids(FFA).Hepatic integrinαvβ3 expression was analyzed in rabbits fed a high-fat diet(HFD)and in rats fed a high-fat,high-carbohydrate diet(HFCD).After synthesis,cyclic arginine-glycine-aspartic acid peptide(cRGD)was labeled with gadolinium(Gd)and used as a contrast agent in magnetic resonance imaging(MRI)performed on mice fed with HFCD.RESULTS Integrinαvβ3 was markedly expressed on FFA-cultured hepatocytes,unlike the control hepatocytes.Hepatic integrinαvβ3 expression significantly increased in both HFD-fed rabbits and HFCD-fed rats as simple fatty liver(FL)progressed to steatohepatitis.The distribution of integrinαvβ3 in the liver of NASH cases largely overlapped with albumin-positive staining areas.In comparison to mice with simple FL,the relative liver MRI-T1 signal value at 60 minutes post-injection of Gd-labeled cRGD was significantly increased in mice with steatohepatitis(P<0.05),showing a positive correlation with the NAFLD activity score(r=0.945;P<0.01).Hepatic integrinαvβ3 expression was significantly upregulated during NASH development,with hepatocytes being the primary cells expressing integrinαvβ3.CONCLUSION After using Gd-labeled cRGD as a tracer,NASH was successfully distinguished by visualizing hepatic integrinαvβ3 expression with MRI.
基金the National Natural Science Foundation of China,No. 30870849,81071068the Science and Technology Planning Project of Guangdong Province,No. 2009B030801101
文摘Previous studies of integrin αvβ3 have focused on ischemic brain damage, although the role of integrin αvβ3 in ischemic preconditioning （IP） has rarely been reported. The present study analyzed the effects of IP on integrin αvβ3 mRNA expression following cerebral ischemia through the use of hematoxylin-eosin staining and real-time quantitative polymerase chain reaction techniques. Integrin avid3 mRNA expression in the ischemia group peaked at 24 hours after ischemia-reperfusion. In the IP ＋ ischemia group, integrin αvβ3 mRNA expression increased after 24 hours, but remained significantly less than the ischemia group, and expression continued to increase until 7 days after ischemiaJreperfusion. These results demonstrate that IP effectively attenuated upregulation of integrin αvβ3 mRNA expression at 24 hours after ischemia.
文摘目的:探讨罗汉果皂苷V(MV)对铁死亡诱导剂RAS选择性致死分子3(RSL3)诱导的人神经母细胞瘤SH-SY5Y细胞铁死亡的抑制作用及可能机制。方法:用RSL3诱导SH-SY5Y细胞建立铁死亡模型。MTT法检测细胞活力;倒置显微镜观察细胞形态;亚铁离子荧光探针FerroFarRed检测细胞内亚铁离子含量;线粒体红色荧光探针MitoTracker Red CMXRos检测线粒体膜电位(MMP);超氧化物阴离子荧光探针二氢乙啶和线粒体超氧化物红色荧光探针MitoSoX Red分别检测细胞内和线粒体内活性氧(ROS)。微板法检测细胞谷胱甘肽(GSH)和丙二醛(MDA)水平。Western blot检测脂酰辅酶A合成酶长链家族成员4(ACSL4)、环加氧酶2(COX-2、)谷胱甘肽过氧化物酶4(GPX4)和溶质载体家族7成员11(SLC7A11)蛋白表达水平。分子对接技术预测MV与ACSL4、COX-2、GPX4和SLC7A11的靶向关系。结果:与control组相比,RSL3组SH-SY5Y细胞活力显著降低(P<0.01),细胞内亚铁离子含量、细胞内和线粒体内ROS水平及MDA水平显著升高(P<0.05或P<0.01),MMP和GSH水平显著降低(P<0.01),ACSL4和COX-2蛋白表达水平显著升高,而GPX4和SLC7A11蛋白表达水平显著降低(P<0.01),提示成功建立了细胞铁死亡模型。MV处理使细胞活力显著升高(P<0.05),细胞内亚铁离子含量、细胞内和线粒体内ROS水平及MDA水平显著降低(P<0.01),MMP和GSH水平显著升高(P<0.05或P<0.01);ACSL4和COX-2蛋白水平显著降低,而GPX4和SLC7A11蛋白水平显著升高(P<0.05或P<0.01)。分子对接结果显示,MV与铁死亡核心蛋白ACSL4、COX-2、GPX4和SLC7A11存在结合位点。结论:MV可抑制RSL3诱导的SH-SY5Y细胞铁死亡的发生,其机制可能与激活SLC7A11/GPX4和抑制ACSL4/COX-2有关。
