Autophagy regulates Endothelial-Mesenchymal transition by decreasing the phosphorylation level of Smad3
Autophagy regulates Endothelial-Mesenchymal transition by decreasing the phosphorylation level of Smad3
复制标题
自噬通过降低 Smad3 的磷酸化水平来调节内皮-间质转化。
DOI：
10.1016/j.bbrc.2017.04.130
复制
发表时间：
2017-06-03
影响因子：
3.1
通讯作者：
Yuan, Fei
中科院分区：
文献类型：
--
作者：
Wang, Jing;Feng, Yifan;Yuan, Fei
转化生长因子-β2(TGF-β2)诱导多种细胞的内皮-间充质转化(EndoMT)和自噬。以往的研究表明，自噬的激活可能会降低转化生长因子-β2诱导的内源性MT。然而，确切的作用仍不清楚。在本研究中，我们发现转化生长因子-β2可诱导人视网膜微血管内皮细胞(HRMECs)发生内源性MT和自噬。用雷帕霉素或海藻糖激活自噬可以减少Snail的表达，表明自噬通过转录和转录后机制调节蜗牛的生产。免疫共沉淀法(COLP)显示LC3与Smad3共沉淀，Western印迹显示自噬诱导剂雷帕霉素和海藻糖可降低Smad3的磷酸化水平。因此，我们的结果表明，自噬通过降低Smad3的磷酸化水平来抵消由转化生长因子-β2触发的内源性MT过程。(C)2017 Elsevier Inc.保留所有权利。
Transforming growth factor-beta2 (TGF-beta 2) induces Endothelial-Mesenchymal transition (EndoMT) and autophagy in a variety of cells. Previous studies have indicated that activation of autophagy might decrease TGF-beta 2 induced EndoMT. However, the precise role remains unclear. In the present study, we found that TGF-beta 2 could induce EndoMT and autophagy in human retinal microvascular endothelial cells (hRMECs). Activation of autophagy by Rapamycin or Trehalose could reduce the expression of Snail, demonstrating a role of autophagy in regulating Snail production both by transcriptional and post transcriptional mechanism. Co-immunoprecipitation (ColP) demonstrated that LC3 coimmunoprecipitated with Smad3 and western blot showed that autophagy inducers, Rapamycin and Trehalose, could decrease the phosphorylation level of Smad3. Therefore, our results demonstrate that autophagy counteracts the EndoMT process triggered by TGF-beta 2 by decreasing the phosphorylation level of Smad3. (C) 2017 Elsevier Inc. All rights reserved.