内皮细胞成纤维生长因子受体1缺陷所致EndMT调控TGFβ信号通路诱导上皮细胞EMT  

Endothelial FGFR1 deficiency induces AcSDKP-resistant EndMT by regulating TGFβsignal pathway

作　　者：胡琼英[1] 艾承锦[1] 陈高莉 熊大迁[1] Hu Qiongying;Ai Chengjin;Chen Gaolin;Xiong Daqian(Department of Laboratory Medicine,Teaching Hospital of Chengdu University of T.C.M,Chengdu 610072,China)

机构地区：[1]成都中医药大学附属医院检验科,610072

出　　处：《中华内分泌代谢杂志》2019年第11期969-972,共4页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金(81601835);四川省科技厅面上项目(18YYJC0689);四川省卫生计生委项目(18ZD039)。

摘　　要：目的 探索成纤维生长因子受体1(fibroblast growth factor receptor 1,FGFR1)调控血管内皮细胞内皮-间充质转化(endothelial-to-mesenchymal transition,EndMT)影响肾小管上皮细胞上皮-间充质转化(epithelial-to-mesenchymal transition,EMT)的作用,以期为糖尿病肾纤维化血管内皮的功能研究提供新的靶点.方法 成纤维生长因子受体底物2(FRS2)siRNA(FRS2siRNA)下调人皮肤微血管内皮细胞(HMVECs)FGF/FGFR1信号通路导致EndMT发生,转移该培养基培养HK2上皮细胞后,用Western印迹法和细胞免疫荧光(immunofluorescence staining)技术检测内皮细胞EndMT、EMT标志物及转化生长因子β(transforming growth factor,TGFβ)信号通路靶点的表达情况.结果 FGFR1缺陷后,可引起内皮细胞TGFβ信号通路上调,从而导致HMVECs的EndMT;HMVECs发生EndMT后的培养基可以诱导HK2的EMT标志物表达增加、TGFβ信号通路激活.结论 内皮FGFR1缺陷诱导的EndMT依赖于TGFβ信号转导诱导相邻上皮细胞中发生EMT;内皮细胞FGFR1是维持内皮稳态和上皮稳态的重要分子,是抗糖尿病肾纤维化的关键靶点.Objective To investigate the role of fibroblast growth factor receptor(FGFR)1 in endothelial to-mesenchymal transition(EndMT)and epithelial-to-mesenchymal transition(EMT),and to find out a new strategy to study the vascular endothelial function of diabetic renal fibrosis.Methods Culture media from FRS2 knockdown HMVECs was transferred to HK-2 cells.Western blot and immunofluorescence staining were used to measure EMT markers and key moleculars of transforming growth factor(TGFβ).Results It was found that the medium from FRS2 siRNA-transfected HMVECs reduced E-cadherin protein levels,increased EMT markers levels,and activated TGFβsignal pathway in HK-2 cells.Conclusion Endothelial FGFR1 deficiency-induced EndMT leads to EMT in neighboring cells in a manner dependent on TGFβ1 signaling.Endothelial cell FGFR1 is an important molecule for maintaining endothelial homeostasis and epithelial homeostasis,and seems to be a key target for anti-diabetic renal fibrosis.

关 键 词：成纤维生长因子受体1 内皮-间充质转化 上皮-间充质转化 糖尿病肾病 

分 类 号：R73[医药卫生—肿瘤]