This was demonstrated by the findings that silencing GPX4 restored high levels of 4-HNE, TFR1 and the severity of renal fibrosis in the UUO kidney of Smad3 KO mice and TGF-β1-treated Smad3 KO MEFs and HK-2 cells treated with SIS3. This evidence concerns the gene SMAD3 and renal fibrosis.