AUTHOR=Wang Dezhong , Zhao Tianyang , Zhao Yushuo , Yin Yuan , Huang Yuli , Cheng Zizhao , Wang Beibei , Liu Sidan , Pan Minling , Sun Difei , Wang Zengshou , Zhu Guanghui 

TITLE=PPARγ Mediates the Anti-Epithelial-Mesenchymal Transition Effects of FGF1ΔHBS in Chronic Kidney Diseases via Inhibition of TGF-β1/SMAD3 Signaling

JOURNAL=Frontiers in Pharmacology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2021.690535

DOI=10.3389/fphar.2021.690535

ISSN=1663-9812

ABSTRACT=<p>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<sup>ΔHBS</sup>) inhibited podocyte EMT, depletion, renal fibrosis, and preserved renal function in two nephropathy models. Mechanistic studies revealed that the inhibitory effects of FGF1<sup>ΔHBS</sup> podocyte EMT were mediated by decreased expression of transforming growth factor β1 via upregulation of PPARγ. FGF1<sup>ΔHBS</sup> enhanced the interaction between PPARγ and SMAD3 and suppressed SMAD3 nuclei translocation. We found that the anti-EMT activities of FGF1<sup>ΔHBS</sup> were independent of glucose-lowering effects. These findings expand the potential uses of FGF1<sup>ΔHBS</sup> in the treatment of diseases associated with EMT.</p>