Huang Chunkai, Meng Mingyao, Li Shuo, Liu Shiyuan, Li Lin, Su Yanjun, Gao Hui, He Shan, Zhao Yiyi, Zhang Min, Hou Zongliu, Wang Wenju, Wang Xiaodan
Scientific Research Department, Yan'an Hospital Affiliated to Kunming Medical University, Kunming, China.
Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, China.
Front Cell Dev Biol. 2022 Apr 5;10:876054. doi: 10.3389/fcell.2022.876054. eCollection 2022.
The therapeutic effects and mechanism of umbilical cord mesenchymal stem cells (UC-MSC) on kidney injury in MRL/Ipr mice were studied. UC-MSC, methylprednisolone (MP), and their combination were used to treat MRL/Ipr mice. The therapeutic effects were evaluated by renal function assessment, and HE, PAS, and Masson staining were carried out on renal tissues and visualized by electron microscopy. Subsequently, podocyte injury was detected by the presence of podocin in renal tissues by immunofluorescence. To further explore the mechanism, serum TGF-β1 was measured, and TGF-β1, p-Smad3, and TRAF6 in the renal tissue were detected by Western blotting. , TGF-β1 was used to stimulate podocytes, and the podocyte activity and changes in synaptopodin were observed after UC-MSC treatment. Significant improvements in renal function and pathological injury were observed in the UC-MSC group compared to the lupus nephritis (LN) model group. UC-MSC and MP treatment improved podocyte injury in MRL/Ipr mice. Western blot examination showed a significant increase in TGF-β1, p-Smad3, and TRAF6 expression in renal tissues of the LN model group, while significant downregulation of those proteins was observed in the UC-MSC group. After TGF-β1 stimulation , podocyte activity decreased, and UC-MSC treatment improved podocyte activity and restored synaptopodin expression. UC-MSC therapy could improve the deterioration of renal function and the pathological changes of the renal tissues in MRL/Ipr mice. Our study suggested that UC-MSC may improve kidney injury and podocyte injury in LN mice by inhibiting the TGF-β1 pathway.
研究了脐带间充质干细胞（UC-MSC）对MRL/Ipr小鼠肾损伤的治疗效果及机制。使用UC-MSC、甲泼尼龙（MP）及其联合用药治疗MRL/Ipr小鼠。通过肾功能评估来评价治疗效果，并对肾组织进行苏木精-伊红（HE）、过碘酸雪夫（PAS）和Masson染色，并用电子显微镜观察。随后，通过免疫荧光检测肾组织中足细胞标志物蛋白的存在来检测足细胞损伤。为进一步探究机制，检测血清转化生长因子-β1（TGF-β1）水平，并通过蛋白质免疫印迹法检测肾组织中TGF-β1、磷酸化Smad3（p-Smad3）和肿瘤坏死因子受体相关因子6（TRAF6）。用TGF-β1刺激足细胞，观察UC-MSC处理后足细胞活性及突触素的变化。与狼疮性肾炎（LN）模型组相比，UC-MSC组的肾功能和病理损伤有显著改善。UC-MSC和MP治疗改善了MRL/Ipr小鼠的足细胞损伤。蛋白质免疫印迹检查显示，LN模型组肾组织中TGF-β1、p-Smad3和TRAF6表达显著增加，而UC-MSC组这些蛋白显著下调。TGF-β1刺激后，足细胞活性降低，UC-MSC处理改善了足细胞活性并恢复了突触素表达。UC-MSC治疗可改善MRL/Ipr小鼠肾功能恶化及肾组织病理变化。我们的研究表明，UC-MSC可能通过抑制TGF-β1通路改善LN小鼠的肾损伤和足细胞损伤。
