TGFβ1 accelerated the progression of diabetic nephropathy via up-regulating BRD4/Notch1/YAP signaling induced fibrosis and proliferation in fibroblasts.

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.