Abstract

Renal injury leads to chronic kidney disease for which women are not only more likely to be diagnosed with than men but have poorer outcomes as well. We have previously shown that expression of Sprr2f, a member of the Small Proline Rich Region (Sprr) gene family, is increased several hundred-fold after renal injury using a unilateral ureteral obstruction (UUO) mouse model. To better understand the role of Sprr2f in renal injury, we generated a Sprr2f knockout (Sprr2f-KO) mouse model using CRISPR-Cas9 technology. Sprr2f-KO female mice showed greater renal damage after UUO compared to wild type (Sprr2f-WT) animals, evidenced by higher hydroxyproline levels and denser collagen staining, indicating a protective role of Sprr2f during renal injury. Gene expression profiling by RNA-seq identified 162 genes whose expression levels were significantly different between day 0 and day 5 after UUO in Sprr2f-KO mice. Out of the 162 genes, 121 were upregulated after UUO and enriched with those involved in oxidation-reduction, a phenomenon not observed in wild type animals, suggesting a protective role of Sprr2f in UUO through defense against oxidative damage. Consistently, bilateral ischemia reperfusion injury resulted in higher serum blood urea nitrogen level and higher tissue reactive oxygen species (ROS) in Sprr2f-KO compared to Sprr2f-WT female mice. Moreover, cultured renal epithelial cells from Sprr2f-KO female mice showed lower viability after oxidative damage induced by menadione compared to Sprr2f-WT cells that could be rescued by supplementation with reduced glutathione, suggesting that Sprr2f induction after renal damage acts as a defense against ROS.

View details for DOI 10.1152/ajprenal.00318.2020

View details for PubMedID 33017192