Chao Chia-Ter, Kuo Feng-Chih, Lin Shih-Hua
Nephrology division, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Nephrology division, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan.
Division of Endocrinology, Department of Internal Medicine, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.
Semin Cell Dev Biol. 2024 Feb 15;154(Pt C):305-315. doi: 10.1016/j.semcdb.2022.09.012. Epub 2022 Oct 12.
Chronic kidney disease (CKD) and its complications, including vascular senescence and progressive renal fibrosis, are associated with inflammation. Vascular senescence, in particular, has emerged as an instrumental mediator of vascular inflammation that potentially worsens renal function. Epigenetically regulated inflammation involving histone modification, DNA methylation, actions of microRNAs and other non-coding RNAs, and their reciprocal reactions during vascular senescence and inflammaging are underappreciated. Their synergistic effects can contribute to CKD progression. Vascular senotherapeutics or pharmacological anti-senescent therapies based on epigenetic machineries can therefore be plausible options for ameliorating vascular aging and even halting the worsening of renal fibrosis. These include histone deacetylase modulators, histone methyltransferase modulators, other histone modification effectors, DNA methyltransferase inhibitors, telomerase reverse transcriptase enhancers, microRNA mimic delivery, and small molecules with microRNA-regulating potentials. Some of these molecules have already been tested and have shown anecdotal evidence for treating uremic vasculopathy and renal fibrosis, supporting the feasibility of this approach.
慢性肾脏病（CKD）及其并发症，包括血管衰老和进行性肾纤维化，都与炎症相关。尤其是血管衰老，已成为血管炎症的一个重要介导因素，可能会使肾功能恶化。涉及组蛋白修饰、DNA甲基化、微小RNA和其他非编码RNA的作用及其在血管衰老和炎症衰老过程中的相互反应的表观遗传调控炎症尚未得到充分认识。它们的协同作用会促使CKD进展。因此，基于表观遗传机制的血管衰老疗法或药理学抗衰老疗法可能是改善血管衰老甚至阻止肾纤维化恶化的合理选择。这些疗法包括组蛋白去乙酰化酶调节剂、组蛋白甲基转移酶调节剂、其他组蛋白修饰效应物、DNA甲基转移酶抑制剂、端粒酶逆转录酶增强剂、微小RNA模拟物递送以及具有微小RNA调节潜力的小分子。其中一些分子已经经过测试，并显示出治疗尿毒症血管病变和肾纤维化的初步证据，支持了这种方法的可行性。
