Sprr2f protects against renal injury by decreasing the level of reactive oxygen species in female mice

Renal injury leads to chronic kidney disease, with which women are not only more likely to be diagnosed than men but have poorer outcomes as well. We have previously shown that expression of small proline-rich region 2f ( ), a member of the small proline-rich region ( ) gene family, is increased several hundredfold after renal injury using a unilateral ureteral obstruction (UUO) mouse model. To better understand the role of in renal injury, we generated a knockout ( -KO) mouse model using CRISPR-Cas9 technology. -KO female mice showed greater renal damage after UUO compared with wild-type ( -WT) animals, as evidenced by higher hydroxyproline levels and denser collagen staining, indicating a protective role of during renal injury. Gene expression profiling by RNA sequencing identified 162 genes whose expression levels were significantly different between and after UUO in -KO mice. Of the 162 genes, 121 genes were upregulated after UUO and enriched with those involved in oxidation-reduction, a phenomenon not observed in -WT animals, suggesting a protective role of in UUO through defense against oxidative damage. Consistently, bilateral ischemia-reperfusion injury resulted in higher serum blood urea nitrogen levels and higher tissue reactive oxygen species in -KO compared with -WT female mice. Moreover, cultured renal epithelial cells from -KO female mice showed lower viability after oxidative damage induced by menadione compared with -WT cells that could be rescued by supplementation with reduced glutathione, suggesting that induction after renal damage acts as a defense against reactive oxygen species.