Department of Physiology, School of Medicine, Tulane University, New Orleans, Louisiana, United States.
Am J Physiol Renal Physiol. 2023 Nov 1;325(5):F578-F594. doi: 10.1152/ajprenal.00091.2023. Epub 2023 Aug 10.
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.
随着高血压、心脏病、糖尿病和肥胖症的发病率不断上升，以及人口老龄化，社会中肾脏疾病的发病率也在不断上升。慢性肾脏病（CKD）的主要特征是持续的炎症、纤维化和肾功能逐渐丧失，导致肾衰竭。性别是导致 CKD 发病率和进展差异的已知因素之一。表观遗传编程是肾脏生理学的重要调节剂，它与肾脏损伤和纤维化的病理生理学密切相关。表观遗传信号将内在和外在信号整合到基因组上，各种环境和激素刺激，包括性激素，调节基因表达和下游细胞反应。在肾脏损伤中起关键作用的最广泛研究的表观遗传改变包括组蛋白修饰和 DNA 甲基化。值得注意的是，这些表观遗传改变是可逆的，这使它们成为治疗肾脏疾病的潜在治疗靶点的候选者。在这里，我们将总结性别对肾脏纤维化和炎症的表观遗传调控差异的现有知识，并强调一些可能的针对 CKD 治疗的表观遗传治疗策略。
