Human umbilical cord mesenchymal stem cell attenuates renal fibrosis via TGF-β/Smad signaling pathways in vivo and in vitro
Human umbilical cord mesenchymal stem cell attenuates renal fibrosis via TGF-β/Smad signaling pathways in vivo and in vitro
复制标题
人脐带间充质干细胞通过 TGF-β/Smad 信号通路在体内和体外减轻肾纤维化
DOI：
10.1016/j.ejphar.2020.173343
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发表时间：
2020
影响因子：
5
通讯作者：
Guanghui Wei
中科院分区：
文献类型：
--
作者：
Yihang Yu;Dong Hu;Yu Zhou;Han Xiang;Bo Liu;Lianju Shen;Chunlan Long;Xing Liu;Tao Lin;Dawei He;Yuanyuan Zhang;Tao Xu;Deying Zhang;Guanghui Wei
肾纤维化是一个渐进的病理过程，最终导致终末期肾衰竭，治疗选择有限。本研究旨在探讨人脐带间充质干细胞（ucMSCs）对肾纤维化的保护作用。分别将UcMSCs静脉注射入马兜铃酸（AA）诱导的肾纤维化小鼠体内，并与转化生长因子β1（TGF-β1）诱导的HK-2细胞共培养。以干细胞治疗组和生理盐水对照组为研究对象，检测各组大鼠的血清肌酐（Scr）、血尿素氮（BUN）水平及肾组织病理学变化。采用免疫组化、免疫荧光和Western blot方法检测上皮间质转化（EMT）相关蛋白和TGF-β/Smad信号通路的表达。结果表明，ucMSCs能有效改善AA大鼠的肾功能和病理结构，减少AA诱导的肾纤维化和细胞外基质沉积。与对照组相比，UcMSCs能显著抑制AA诱导的小鼠和TGF-β1诱导的HK-2细胞的EMT过程和TGF-β1/Smad信号通路（p < 0.05）。提示ucMSCs通过抑制TGF-β1/Smad信号通路的激活发挥抗纤维化的肾单位保护作用。
Renal fibrosis is a progressive pathological process that eventually leads to end-stage renal failure with limited therapeutic options. The aim of this study was to investigate the nephron-protective effect of human umbilical cord mesenchymal stem cells (ucMSCs) on renal fibrosis. UcMSCs were intravenously injected into renal fibrosis mice induced by aristolochic acid (AA) and co-cultured with HK-2 cells induced by TGF-β1, respectively. The kidney functions including serum creatinine (Scr) and blood urea nitrogen (BUN) levels, and histopathology were examined after treated with stem cells and normal saline as control. Immunohistochemical staining, immunofluorescent staining, and Western blot analysis were used to assessed the expression of proteins associated with epithelial to mesenchymal transition (EMT) and TGF-β/Smad signaling pathway. The results showed that ucMSCs effectively improved the kidney function and pathological structure, reduced AA-induced fibrosis and extracellular matrix deposition. Besides, UcMSCs significantly inhibited the EMT process and TGF-β1/Smad signaling pathway in AA-induced mice and TGF-β1-induced HK-2 cells compared to the control (p < 0.05). Our data suggested that ucMSCs play as a nephron-protective role in anti-fibrosis through inhibiting the activation of TGF-β1/Smad signaling pathway.