PRDM16 acts as a therapeutic downstream target of TGF-β signaling in chronic kidney disease.

ABSTRACT: Transforming growth factor β (TGF-β) signaling is the master modulator of renal fibrosis. However, targeting drugs have failed to prevent the progression of chronic kidney disease (CKD) in clinical trials due to the extensive biological regulation of TGF-β signaling. It is necessary to investigate the precise downstream mechanisms of TGF-β signaling that regulate renal fibrosis. In this study, we found that PR-domain containing 16 (PRDM16) expression in human renal tubular epithelial cells was markedly reduced by TGF-β. Mechanistically, activated Smad3 induced by TGF-β interacted with the cofactor H-Ras and bound to the promoter of PRDM16, downregulating its transcription. Tubular-specific knockout of Prdm16 promoted renal fibrosis in models of unilateral ureteral occlusion (UUO) and unila

SUBMITTER: Yuan Q 

PROVIDER: S-EPMC12487692 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature