Human umbilical cord mesenchymal stem cell conditioned medium attenuates renal fibrosis by reducing inflammation and epithelial-to-mesenchymal transition via the TLR4/NF-κB signaling pathway in vivo and in vitro.
Human umbilical cord mesenchymal stem cell conditioned medium attenuates renal fibrosis by reducing inflammation and epithelial-to-mesenchymal transition via the TLR4/NF-κB signaling pathway in vivo and in vitro.
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人脐带间充质干细胞条件培养基在体内和体外通过TLR4/NF-κB信号通路减少炎症和上皮向间充质转化，从而减轻肾纤维化。
DOI：
10.1186/s13287-017-0760-6
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发表时间：
2018-01-12
影响因子：
7.5
通讯作者：
Wei G
中科院分区：
文献类型：
--
作者：
Liu B;Ding F;Hu D;Zhou Y;Long C;Shen L;Zhang Y;Zhang D;Wei G
肾纤维化的特征是间质炎性细胞浸润和炎性介质的释放、成纤维细胞的活化和增殖以及过量的细胞外基质（ECM）沉积。本研究旨在评价人脐带间充质干细胞（hucMSC）条件培养液（CM）对肾小管间质炎症和纤维化的影响。采用单侧输尿管梗阻（UUO）模型，在体内制备肾间质纤维化模型。将大鼠随机分为Sham组、Sham + CM组、UUO组、UUO + CM组。通过检测肾组织病理学、血清肌酐（SCr）和血尿素氮（BUN）来评价hucMSC-CM对UUO所致肾损伤的影响。ELISA法检测血清和肾组织中TNF-α、IL-6和IL-1β的水平。采用免疫组化染色和蛋白质印迹法检测肾组织纤维化和炎症相关蛋白的表达。通过免疫荧光染色、ELISA和蛋白质印迹研究hucMSC-CM对TGF-β1诱导的上皮-间质转化（EMT）过程和NRK-52 E细胞中的炎症的影响。hucMSC-CM减少了UUO诱导的肾纤维化中细胞外基质沉积和炎性细胞浸润以及炎性因子的释放。此外，hucMSC-CM显著减弱了UUO和TGF-β1诱导的NRK-52 E细胞大鼠的EMT过程和促炎细胞因子。hucMSC-CM还在体内和体外抑制TLR 4/NF-κB信号通路。我们的研究结果表明hucMSC-CM对UUO诱导的肾纤维化具有保护作用，并且hucMSC-CM通过抑制TLR 4/NF-κB信号通路活化而发挥其抗炎作用。本文的在线版本（doi：10.1186/s13287-017-0760-6）包含补充材料，可供授权用户使用。
Renal fibrosis is characterized by infiltration of interstitial inflammatory cells and release of inflammatory mediators, activation and proliferation of fibroblasts, and deposition of excessive extracellular matrix (ECM). The aim of this study was to evaluate the effect of human umbilical cord-derived mesenchymal stem cell (hucMSC) conditioned medium (CM) on renal tubulointerstitial inflammation and fibrosis. Renal interstitial fibrosis was prepared in vivo using the unilateral ureteral obstruction (UUO). Rats were divided randomly into Sham group, Sham group with CM, UUO group, and UUO group with CM. The effect of hucMSC-CM on kidney injury induced by UUO was assessed by detecting kidney histopathology, serum creatinine (SCr), and blood urea nitrogen (BUN). The levels of TNF-α, IL-6, and IL-1β in serum and kidney tissues were detected by ELISA. The expression of proteins associated with fibrosis and renal inflammation was investigated using immunohistochemical staining and western blotting. The effects of hucMSC-CM on the TGF-β1-induced epithelial–mesenchymal transition (EMT) process and on inflammation in NRK-52E cells were investigated by immunofluorescent staining, ELISA, and western blotting. hucMSC-CM reduced extracellular matrix deposition and inflammatory cell infiltration as well as release of inflammatory factors in UUO-induced renal fibrosis. Furthermore, hucMSC-CM markedly attenuated the EMT process and proinflammatory cytokines in rats with UUO and TGF-β1-induced NRK-52E cells. hucMSC-CM also inhibited the TLR4/NF-κB signaling pathway in vivo and in vitro. Our results suggest that hucMSC-CM has protective effects against UUO-induced renal fibrosis and that hucMSC-CM exhibits its anti-inflammatory effects through inhibiting TLR4/NF-κB signaling pathway activation. The online version of this article (doi:10.1186/s13287-017-0760-6) contains supplementary material, which is available to authorized users.
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影响因子：
11
作者：
Wang LT;Ting CH;Yen ML;Liu KJ;Sytwu HK;Wu KK;Yen BL
通讯作者：
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