Abstract：
Induced pluripotent stem cells (iPSCs) have been the focus of cellular therapy studies. The use of iPSCs in regenerative medicine is limited by their tumorigenic potential. This study sought to determine whether iPSCs-derived podocytes attenuate acute kidney injury (AKI) and the molecular mechanism. Inoculation of iPSCs-podocytes significantly promoted the repair of kidney injury in AKI mice, reduced the levels of kidney injury factors Scr, BUN, and urinary NAG, and alleviated the inflammatory response. Histological analysis revealed a significant increase in the number of M2 macrophages and a significant decrease in M1 macrophages in the kidney tissues. Subsequently, the genes and signaling pathways that may be associated with kidney injury repair in mice were analyzed by RNA-seq and bioinformatics prediction. The polarization of M2 macrophages was promoted by MAF bZIP transcription factor B (Mafb)-mediated activation of C-C motif chemokine receptor 5 (Ccr5) and nicotinamide phosphoribosyltransferase (Nampt) signaling pathway. Taken together, these results show that iPSCs-podocytes depend on Mafb to activate the Nampt signaling pathway through transcriptional activation of Ccr5, thereby promoting the repair of AKI caused by ischemia-reperfusion.
摘要：
诱导多能干细胞(iPSC)一直是细胞治疗研究的焦点。iPSC在再生医学中的使用受到其致瘤潜力的限制。本研究旨在确定iPSC来源的足细胞是否减轻急性肾损伤（AKI）及其分子机制。接种iPSCs-足细胞可显著促进AKI小鼠肾损伤的修复,降低肾损伤因子Scr的水平，BUN,和尿NAG，减轻炎症反应。组织学分析显示，肾脏组织中M2巨噬细胞的数量显着增加，M1巨噬细胞的数量显着减少。随后，通过RNA-seq和生物信息学预测分析了可能与小鼠肾损伤修复相关的基因和信号通路。MAFbZIP转录因子B（Mafb）介导的C-C基序趋化因子受体5（Ccr5）和烟酰胺磷酸核糖基转移酶（Nampt）信号通路的激活促进了M2巨噬细胞的极化。一起来看,这些结果表明，iPSCs-足细胞依赖于Mafb通过转录激活Ccr5激活Nampt信号通路，从而促进缺血再灌注引起的AKI的修复。
