Li Lin, Zhang Limin, Li Zhe, Wang Qian, Zhang Qian, Li Song, Ji Juan
Nephrology Department, Affiliated Hospital of Hebei University, No. 212 Yuhua East Road, Baoding, 071000, Hebei, China.
Key Laboratory of Bone Metabolism and Physiology in Chronic Kidney Disease of Hebei Province, Affiliated Hospital of Hebei University, No. 212 Yuhua East Road, Baoding, 071000, Hebei, China.
Sci Rep. 2025 Jul 13;15(1):25338. doi: 10.1038/s41598-025-10143-6.
Mounting evidence implicates transforming growth factor-β1 (TGF-β1)-mediated renal tubular cell apoptosis in the pathogenesis of diabetic nephropathy. This investigation sought to elucidate the molecular mechanisms governing the pathogenic role of TGF-β1 in diabetic nephropathy progression. In vitro, human renal fibroblasts purchased were divided into six groups after different stimuli. Western blot was used to observe the cell protein expression, and CCK-8 was used to observe cell proliferation. In the in vivo experiment, 32 SD male rats were randomly divided into Control group, Model group, Model + TGFβ1 group, and Model + TGFβ1 + Notch1-KD group, and Model group was experimentally induced by a high-fat diet (HFD)/streptozocin(STZ) regimen in type 2 diabetes mellitus ( T2DM ) mouse model. HE staining was used to observe the degree of renal tissue fibrosis, and Western blot was used to observe the protein expression in renal tissues. In the in vitro experiment, TGFβ1 induced fibrosis and fibroblast proliferation by regulating the BRD4/Notch1/YAP signaling pathway. In the in vivo experiment, it was found that diabetic nephropathy rats treated with TGFβ1 showed significantly increased renal tissue fibrosis; when Notch1 was knocked down, the renal tissue fibrosis in diabetic nephropathy rats was significantly reduced. TGFβ1 accelerates the progression of diabetic nephropathy by inducing fibrosis and fibroblast proliferation through the regulation of the BRD4/Notch1/YAP signaling pathway.
越来越多的证据表明，转化生长因子-β1（TGF-β1）介导的肾小管细胞凋亡在糖尿病肾病的发病机制中起作用。本研究旨在阐明TGF-β1在糖尿病肾病进展中的致病作用的分子机制。在体外，将购买的人肾成纤维细胞在不同刺激后分为六组。采用蛋白质免疫印迹法观察细胞蛋白表达，采用CCK-8法观察细胞增殖。在体内实验中，将32只SD雄性大鼠随机分为对照组、模型组、模型+TGFβ1组、模型+TGFβ1+Notch1-KD组，模型组采用高脂饮食（HFD）/链脲佐菌素（STZ）方案诱导建立2型糖尿病（T2DM）小鼠模型。采用苏木精-伊红（HE）染色观察肾组织纤维化程度，采用蛋白质免疫印迹法观察肾组织蛋白表达。体外实验中，TGFβ1通过调节BRD4/Notch1/YAP信号通路诱导纤维化和成纤维细胞增殖。体内实验发现，TGFβ1治疗的糖尿病肾病大鼠肾组织纤维化明显增加；敲低Notch1后，糖尿病肾病大鼠肾组织纤维化明显减轻。TGFβ1通过调节BRD4/Notch1/YAP信号通路诱导纤维化和成纤维细胞增殖，加速糖尿病肾病的进展。
