Sex-specific epigenetic programming in renal fibrosis and inflammation

The growing prevalence of hypertension, heart disease, diabetes, and obesity along with an aging population is leading to a higher incidence of renal diseases in society. Chronic kidney disease (CKD) is characterized mainly by persistent inflammation, fibrosis, and gradual loss of renal function leading to renal failure. Sex is a known contributor to the differences in incidence and progression of CKD. Epigenetic programming is an essential regulator of renal physiology and is critically involved in the pathophysiology of renal injury and fibrosis. Epigenetic signaling integrates intrinsic and extrinsic signals onto the genome, and various environmental and hormonal stimuli, including sex hormones, which regulate gene expression and downstream cellular responses. The most extensively studied epigenetic alterations that play a critical role in renal damage include histone modifications and DNA methylation. Notably, these epigenetic alterations are reversible, making them candidates for potential therapeutic targets for the treatment of renal diseases. Here, we will summarize the current knowledge on sex differences in epigenetic modulation of renal fibrosis and inflammation and highlight some possible epigenetic therapeutic strategies for CKD treatment.