FTO inhibition attenuates renal fibrosis by downregulating ferroptosis activator ACSL4 and profibrotic factor TGFBI.

ABSTRACT: Renal fibrosis (RF) is the main pathological feature and a potential therapeutic target of chronic kidney disease (CKD), a prevalent health problem causing a high economic burden to the health care system. Fat mass and obesity-associated (FTO) inhibition, either genetically or pharmacologically, significantly reduced collagen deposition, lipid peroxidation, and ferroptosis marker expression after unilateral ureteral obstruction (UUO) compared with sham-operated controls in mice. In murine and human kidney epithelial cells as well as in human embryonic stem cell-derived kidney organoids, FTO inhibition reduced erastin-induced ferroptosis by decreasing lipid peroxidation and reactive oxygen species production by downregulating the ferroptosis driver ACSL4. Moreover, FTO inhibition directly d

SUBMITTER: Zhang D 

PROVIDER: S-EPMC12494575 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature