Department of Urology, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China; Chongqing Key Laboratory of Children Urogenital Department and Tissue Engineering, Chongqing, 400014, China; Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, 400014, China; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing, 400014, China; National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, China; Chongqing Key Laboratory of Pediatrics, Chongqing, 400014, China.
Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27101, USA.
Eur J Pharmacol. 2020 Sep 15;883:173343. doi: 10.1016/j.ejphar.2020.173343. Epub 2020 Jul 3.
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.
肾纤维化是一种进行性的病理过程,最终会导致终末期肾衰竭,治疗选择有限。本研究旨在探讨人脐带间充质干细胞(ucMSCs)对肾纤维化的肾保护作用。分别将 ucMSCs 静脉注射到马兜铃酸(AA)诱导的肾纤维化小鼠和 TGF-β1 诱导的 HK-2 细胞中进行共培养。用干细胞和生理盐水作为对照处理后,检查肾脏功能(包括血清肌酐(Scr)和血尿素氮(BUN)水平)和组织病理学。免疫组织化学染色、免疫荧光染色和 Western blot 分析用于评估与上皮间质转化(EMT)和 TGF-β/Smad 信号通路相关的蛋白表达。结果表明,ucMSCs 有效改善了肾功能和病理结构,减少了 AA 诱导的纤维化和细胞外基质沉积。此外,与对照组相比,ucMSCs 显著抑制了 AA 诱导的小鼠和 TGF-β1 诱导的 HK-2 细胞中的 EMT 过程和 TGF-β1/Smad 信号通路(p<0.05)。我们的数据表明,ucMSCs 通过抑制 TGF-β1/Smad 信号通路的激活在抗纤维化中发挥肾保护作用。