Epigenetics in kidney diseases.
Epigenetics in kidney diseases.
复制标题
肾脏疾病的表观遗传学。
DOI：
10.1016/bs.acc.2020.09.005
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发表时间：
2021
影响因子：
--
通讯作者：
Li, Xiaogang
中科院分区：
文献类型：
--
作者：
Ding, Hao;Zhang, Lu;Yang, Qian;Zhang, Xiaoqin;Li, Xiaogang
表观遗传学检查DNA及其相关蛋白质的遗传变化，但基因序列突变除外。表观遗传调控通过DNA甲基化、染色质修饰（通过表观遗传调控因子和非编码RNA种类）的作用在肾细胞生物学中发挥基础作用。包括急性肾损伤、慢性肾病、糖尿病肾病和肾纤维化在内的肾脏疾病是与甚至在个体肾细胞中的许多分子改变相关的多步骤过程。表观遗传学改变，包括异常DNA甲基化，异常组蛋白改变和microRNA表达的变化都有助于肾脏发病机制。这些变化改变了全基因组表观遗传特征，并破坏了保护肾细胞免受不受控制的生长、凋亡和其他肾相关综合征发展的必要途径。分子变化影响肾细胞内的细胞功能及其微环境，以驱动和维持疾病表型。在本章中，我们简要概述了四种肾脏疾病的表观遗传机制，包括急性肾损伤，慢性肾脏病，糖尿病肾病和肾纤维化。我们主要集中在目前的知识，全基因组分析的DNA甲基化和组蛋白修饰，和表观遗传调控的特定基因（S）在这些疾病的病理生理学和翻译的潜力，确定新的生物标志物和治疗的预防和治疗。将表观基因组检测纳入临床研究对于阐明新型表观遗传生物标志物和使用新兴疗法开发精准医学至关重要。
Epigenetics examines heritable changes in DNA and its associated proteins except mutations in gene sequence. Epigenetic regulation plays fundamental roles in kidney cell biology through the action of DNA methylation, chromatin modification via epigenetic regulators and non-coding RNA species. Kidney diseases, including acute kidney injury, chronic kidney disease, diabetic kidney disease and renal fibrosis are multistep processes associated with numerous molecular alterations even in individual kidney cells. Epigenetic alterations, including anomalous DNA methylation, aberrant histone alterations and changes of microRNA expression all contribute to kidney pathogenesis. These changes alter the genome-wide epigenetic signatures and disrupt essential pathways that protect renal cells from uncontrolled growth, apoptosis and development of other renal associated syndromes. Molecular changes impact cellular function within kidney cells and its microenvironment to drive and maintain disease phenotype. In this chapter, we briefly summarize epigenetic mechanisms in four kidney diseases including acute kidney injury, chronic kidney disease, diabetic kidney disease and renal fibrosis. We primarily focus on current knowledge about the genome-wide profiling of DNA methylation and histone modification, and epigenetic regulation on specific gene(s) in the pathophysiology of these diseases and the translational potential of identifying new biomarkers and treatment for prevention and therapy. Incorporating epigenomic testing into clinical research is essential to elucidate novel epigenetic biomarkers and develop precision medicine using emerging therapies.
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