Description
Female sex protects against development of acute kidney injury (AKI). While sex hormones may be involved in protection, the role of differential gene expression is unknown. We conducted gene profiling in male and female mice with or without kidney ischemia-reperfusion injury. Mice underwent bilateral renal pedicle clamping (30 min), and tissues were collected 24 hours after reperfusion. RNA-sequencing was performed on proximal tubules and kidney endothelial cells. Female mice were resistant to ischemic injury compared to males, determined by plasma creatinine, histologic scores, neutrophil infiltration, and extent of apoptosis. Sham mice had sex-specific gene disparities in proximal tubule and endothelium, and male mice showed profound gene dysregulation with ischemia-reperfusion compared to females. After ischemia proximal tubules from females exhibited smaller increases compared to males in injury-associated genes Lcn2, Havcr1, and Krt18, and no upregulation of Sox9 or Krt20. Endothelial upregulation of adhesion molecules and cytokines/chemokines occurred in males, but not females. Upregulated genes in male ischemic proximal tubules were linked to tumor necrosis factor and Toll-like receptor pathways, while female ischemic proximal tubules showed upregulated genes in pathways related to transport. The data suggest that sex-specific gene expression profiles in male and female proximal tubule and endothelium may underlie disparities in susceptibility to AKI.
Overall Design
Transcriptomic profile of endothelial cells from control (sham) FVB female mice (n=2), sham male mice (n=3), acute kidney injury (AKI) female mice (n=3) and AKI male mice (n=3). The experiment also includes the same experimental groups with samples of proximal tubular cells from sham female mice (n=3), sham male mice(n=3), AKI female mice (n=3) and AKI male mice (n=3); Please note that wwo libraries sequenced from the ‘Sham M PTs rep 3’ and quantified separately (i.e. rep3 and rep3B). Technical replicates combined in DESeq2 analysis
Curator
xm_li