STAT6 contributes to renal fibrosis by modulating PPARα-mediated tubular fatty acid oxidation.

ABSTRACT: Lipid metabolism, especially fatty acid oxidation (FAO) dysfunction, is a major driver of renal fibrosis; however, the detailed regulatory mechanisms involved remain unclear. In this study, we showed that there existed an association between the signal transducer and activator of transcription 6 (STAT6) and tubular lipid metabolism in fibrotic kidneys. Specifically, STAT6 was activated along with the accumulation of lipids via the downregulation of FAO-related genes when mice were subjected to unilateral ureteral obstruction (UUO) or high-fat diet challenge. Tubular-specific depletion, or pharmacologic inhibitor of Stat6 in mice, and Stat6 knockdown in cultured tubular cells attenuated lipid accumulation and renal fibrosis by enhancing FAO. Mechanistically, STAT6 transcriptionally inhibite

SUBMITTER: Li J 

PROVIDER: S-EPMC8770798 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature