Role of endothelial-to-mesenchymal transition induced by TGF-β1 in transplant kidney interstitial fibrosis.
Role of endothelial-to-mesenchymal transition induced by TGF-β1 in transplant kidney interstitial fibrosis.
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TGF-β1 诱导的内皮间质转化在移植肾间质纤维化中的作用。
DOI：
10.1111/jcmm.13157
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发表时间：
2017-10
影响因子：
5.3
通讯作者：
Gu M
中科院分区：
文献类型：
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作者：
Wang Z;Han Z;Tao J;Wang J;Liu X;Zhou W;Xu Z;Zhao C;Wang Z;Tan R;Gu M
肾间质纤维化引起的慢性同种异体移植物功能障碍（CAD）是肾移植失败的主要原因。内皮-间充质转化（EndMT）可能在肾纤维化中起重要作用。因此，我们进行了这项研究，以表征EndMT在移植肾间质纤维化中的功能和潜在机制。用western blotting、qRT - PCR和ELISA检测了转化生长因子β1 （TGF - β1）在不同剂量或不同时间间隔处理的人脐静脉内皮细胞（HUVECs）中与EndMT相关的蛋白和mrna。用细胞运动和迁移试验评价细胞运动和迁移。通过western blotting分析TGF - β1诱导EndMT的各种典型和非典型通路相关因子，确定其机制。此外，对照组和CAD组的人肾组织也采用HE、马氏三色、免疫组织化学、间接免疫荧光双染色和western blotting检测这些蛋白。TGF - β1以时间依赖性和剂量依赖性的方式显著促进EndMT的发展，促进HUVECs的运动和迁移能力。TGF‐β/Smad和Akt/mTOR/p70S6K信号通路与TGF‐β1诱导的EndMT发病机制有关，通过对照组和CAD组的体内标本分析也证实了这一点。EndMT可能通过靶向TGF - β/Smad和Akt/mTOR/p70S6K信号通路促进移植肾间质纤维化，从而导致肾移植受者CAD的发生。
Chronic allograft dysfunction (CAD) induced by kidney interstitial fibrosis is the main cause of allograft failure in kidney transplantation. Endothelial‐to‐mesenchymal transition (EndMT) may play an important role in kidney fibrosis. We, therefore, undertook this study to characterize the functions and potential mechanism of EndMT in transplant kidney interstitial fibrosis. Proteins and mRNAs associated with EndMT were examined in human umbilical vein endothelial cells (HUVECs) treated with transforming growth factor‐beta1 (TGF‐β1) at different doses or at different intervals with western blotting, qRT‐PCR and ELISA assays. Cell motility and migration were evaluated with motility and migration assays. The mechanism of EndMT induced by TGF‐β1 was determined by western blotting analysis of factors involved in various canonical and non‐canonical pathways. In addition, human kidney tissues from control and CAD group were also examined for these proteins by HE, Masson's trichrome, immunohistochemical, indirect immunofluorescence double staining and western blotting assays. TGF‐β1 significantly promoted the development of EndMT in a time‐dependent and dose‐dependent manner and promoted the motility and migration ability of HUVECs. The TGF‐β/Smad and Akt/mTOR/p70S6K signalling pathways were found to be associated with the pathogenesis of EndMT induced by TGF‐β1, which was also proven in vivo by the analysis of specimens from the control and CAD groups. EndMT may promote transplant kidney interstitial fibrosis by targetting the TGF‐β/Smad and Akt/mTOR/p70S6K signalling pathways, and hence, result in the development of CAD in kidney transplant recipients.
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影响因子：
--
作者：
Nagai T;Kanasaki M;Srivastava SP;Nakamura Y;Ishigaki Y;Kitada M;Shi S;Kanasaki K;Koya D
通讯作者：
Koya D
结缔组织疾病中的纤维化：肌纤维细胞和成纤维细胞上皮细胞相互作用的作用。
影响因子：
4.9
作者：
Krieg, Thomas;Abraham, David;Lafyatis, Robert
通讯作者：
Lafyatis, Robert
影响因子：
7.5
作者：
Choi HY;Lee HG;Kim BS;Ahn SH;Jung A;Lee M;Lee JE;Kim HJ;Ha SK;Park HC
通讯作者：
Park HC
影响因子：
6.2
作者：
Djamali A;Samaniego M
通讯作者：
Samaniego M
影响因子：
4.8
作者：
Gäbele, E;Reif, S;Rippe, RA
通讯作者：
Rippe, RA