The bach1/G9a/Slc7a11 axis epigenetically promotes renal fibrosis by mediated ferroptosis

A high percentage of individuals with renal fibrosis are susceptible to developing chronic kidney disease (CKD), and conventional therapy fails to halt the progression of renal fibrosis and CKD. Here, we assessed the potential functions of G9a in a unilateral ureteral obstruction (UUO)-induced renal fibrosis mouse model. The expression of G9a was significantly increased in the fibrotic kidneys of patients and mice. G9a knockout inhibited inflammatory cytokine production and collagen deposition in mice, whereas its overexpression aggravated renal fibrosis in mice. In vitro, the knockdown of G9a alleviated the production of inflammatory cytokines and renal fibrosis. G9a, a histone methyltransferase, interacts with transcription factor Bach1 and activates ferroptosis by suppressing the transcription of Slc7a11 via dimethylation of histone 3 lysine 9 (H3K9me2) both in vivo and in vitro. Collectively, our findings indicate that G9a could be an attractive therapeutic target for renal fibrosis.