Effects of Human Umbilical Cord Mesenchymal Stem Cells on Aristolochic Acid-induced Renal Fibrosis in Mice and Its Mechanism
YU Yihang, ZHANG Deying*, HU Dong, ZHOU Yu, LIU Bo, XIANG Han, LONG Chunlan, SHEN Lianju, LIU Xing, LIN Tao, HE Dawei, WEI Guanghui*
In this study, we investigated the effect of huc-MSC (human umbilical cord mesenchymal stem cell) on AA (aristolochic acid)-induced renal fibrosis in mice and its possible mechanism. We injected huc-MSC into the mouse model of renal fibrosis induced by AA via tail vein injection. HE, PAS and Masson staining were used to observe the renal morphology. Western blot and immunohistochemistry were used to examine the expression of EMT (epithelial to mesenchymal transition) markers including E-cadherin, N-cadherin and proteins of TGF-β/Smad signaling pathway. The results showed that renal fibrosis could be induced by aristolochic acid in mice, which characterized by tubular dilatation and structural destruction, visible collagen fiber deposition in the renal interstitial region. The down-regulation of E-cadherin and up-regulation of the N-cadherin, TGF-β1 and p-Smad2/3 were also detected in the kidney of aristolochic acid-induced fibrotic mice by Western blot and immunohistochemistry. After the intervention of huc-MSC, renal fibrosis was significantly alleviated with the decrease of deposition of collagen fibers. Besides, the expression of E-cadherin was up-regulated, while the expression of N-cadherin and TGF-β1, p-Smad2/3 were reduced. We concluded that renal fibrosis in mice could be induced by aristolochic acid, and huc-MSC could interfere with the process of epithelial to mesenchymal transition by inhibiting TGF-β/Smad signaling pathway and alleviating aristolochic acid-induced renal fibrosis in mice.
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