Enhanced Expression of the Female-Biased Gene Gsta2 in Male Proximal Tubule Cells Improves Renal Resilience to Ischemia-Reperfusion Injury
Background: Genetic sex is an important determinant of renal injury and repair, with female kidneys typically exhibiting greater resilience to acute kidney injury (AKI). Among the sexually dimorphic genes in mouse proximal tubule cells (PTCs), Gsta2, an NRF2-regulated antioxidant enzyme, is strongly enriched in females. Here, we hypothesized that augmenting Gsta2 in male PTCs would enhance resistance to ischemia-reperfusion injury (IRI). Overall design: we performed whole-kidney bulk RNA sequencing (bulk RNA-seq) on kidney tissues 4 hours post ischemia-reperfusion injury (IRI) to capture early events in the injury response by comparing transcriptional profiles between wild-type (WT) and transgenic (TG) kidneys