PPARγ Mediates the Anti-Epithelial-Mesenchymal Transition Effects of FGF1^ΔHBS in Chronic Kidney Diseases via Inhibition of TGF-β1/SMAD3 Signaling.

ABSTRACT: Podocytes are essential components of the glomerular basement membrane. Epithelial-mesenchymal-transition (EMT) in podocytes results in proteinuria. Fibroblast growth factor 1 (FGF1) protects renal function against diabetic nephropathy (DN). In the present study, we showed that treatment with an FGF1 variant with decreased mitogenic potency (FGF1^ΔHBS) inhibited podocyte EMT, depletion, renal fibrosis, and preserved renal function in two nephropathy models. Mechanistic studies revealed that the inhibitory effects of FGF1^ΔHBS podocyte EMT were mediated by decreased expression of transforming growth factor β1 via upregulation of PPARγ. FGF1^ΔHBS enhanced the interaction between PPARγ and SMAD3 and suppressed SMAD3 nuclei translocation. We found that the anti-EMT activities of FGF1^ΔHBS were independent of glucose-lowering effects. These findings expand the potential uses of FGF1^ΔHBS in the treatment of diseases associated with EMT.

SUBMITTER: Wang D 

PROVIDER: S-EPMC8209477 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature