Liu Shiyuan, Meng Mingyao, Huang Chunkai, He Lijia, Wang Pu, Tang Zhe, Ran Xi, Gao Hui, Guo Yangfan, He Yan, Chen Jian, Hu Haiyan, He Shan, Zhao Yiyi, Hou Zongliu, Li Lin, Li Wenhong, Wang Wenju, Wang Xiaodan
Yan'an Hospital Affiliated to Kunming Medical University, Kunming, China.
Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Kunming, China.
J Diabetes Res. 2025 Apr 11;2025:6683126. doi: 10.1155/jdr/6683126. eCollection 2025.
In this study, we investigated the therapeutic effects and mechanisms of umbilical cord mesenchymal stem cells (UCMSCs) in diabetic nephropathy (DN) ZDF (FA/FA) rats. The therapeutic effects were assessed by renal function tests, the urinary albumin-creatinine ratio, PAS staining, electron microscopy, and TGF-1 expression in renal tissue. Subsequently, podocyte injury in renal tissue was detected by immunofluorescence staining for podocin. To further explore the underlying mechanism, serum Angptl4 levels were measured, and Angptl4, integrin 3, fibronectin, and podocin levels in renal tissue were analysed by Western blotting. In vitro, podocytes are stimulated with high glucose and then treated with UCMSCs, and podocyte activity and the expression of synaptopodin, Angptl4, and integrin 3 were observed. UCMSC significantly improve renal function, pathological injury, and podocyte injury in the ZDF (FA/FA) rats. Western blot revealed increased expression of Angptl4, integrin 3, and fibronectin in renal tissues of the DN group, and UCMSC treatment significantly downregulated those proteins. However, UCMSC showed no effects on serum Angptl4 concentration. Podocin expression in renal tissues was significantly restored by UCMSC treatment. In vitro, podocyte activity was decreased after high glucose stimulation and improved by UCMSC treatment. UCMSC restored the expression of synaptopodin, and Angptl4 and downstream integrin 3 were also inhibited. Our study suggested that UCMSC therapy could improve renal function and renal pathological changes in ZDF (FA/FA) rats. In addition, inhibition of the Angptl4/integrin 3 pathway is the potential mechanism by which UCMSC attenuates podocyte injury in the DN model.
在本研究中，我们调查了脐带间充质干细胞（UCMSC）对糖尿病肾病（DN）ZDF（FA/FA）大鼠的治疗作用及机制。通过肾功能测试、尿白蛋白肌酐比值、PAS染色、电子显微镜检查以及肾组织中转化生长因子-1表达来评估治疗效果。随后，通过对足细胞标记蛋白进行免疫荧光染色检测肾组织中的足细胞损伤。为进一步探究潜在机制，检测血清血管生成素样蛋白4（Angptl4）水平，并通过蛋白质免疫印迹法分析肾组织中Angptl4、整合素β3、纤连蛋白和足细胞标记蛋白的水平。在体外，用高糖刺激足细胞，然后用UCMSC进行处理，观察足细胞活性以及突触素、Angptl4和整合素β3的表达。UCMSC显著改善了ZDF（FA/FA）大鼠的肾功能、病理损伤和足细胞损伤。蛋白质免疫印迹显示，DN组肾组织中Angptl4、整合素β3和纤连蛋白的表达增加，而UCMSC治疗显著下调了这些蛋白。然而，UCMSC对血清Angptl4浓度没有影响。UCMSC治疗可显著恢复肾组织中足细胞标记蛋白的表达。在体外，高糖刺激后足细胞活性降低，而UCMSC治疗可使其改善。UCMSC恢复了突触素的表达，并且Angptl4及其下游的整合素β3也受到抑制。我们研究表明，UCMSC治疗可改善ZDF（FA/FA）大鼠的肾功能和肾脏病理变化。此外，抑制Angptl4/整合素β3信号通路是UCMSC减轻DN模型中足细胞损伤的潜在机制。
