In contrast, specifically silencing renal GPX4 in Smad3 KO mice restored the severity of ferroptosis and progressive renal fibrosis to similar levels as seen in Smad3 WT UUO mice including a loss of GPX4 while increasing expression of 4-HNE, TFR1, α-SMA, Col-1, and FN (Figure 6 andFigure S5A). This evidence concerns the gene SMAD3 and renal fibrosis.