Xu Jing, Xue Cheng, Wang Xiaodong, Zhang Lei, Mei Changlin, Mao Zhiguo
Kidney Institute, Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
State Key Laboratory of Cell Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
Front Med (Lausanne). 2022 Jul 5;9:921631. doi: 10.3389/fmed.2022.921631. eCollection 2022.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease worldwide and is one of the major causes of end-stage renal disease. and are two genes that mainly contribute to the development and progression of ADPKD. The precise mechanism is not fully understood. In recent years, epigenetic modification has drawn increasing attention. Chromatin methylation is a very important category of PKD epigenetic changes and mostly involves DNA, histone, and RNA methylation. Genome hypomethylation and regional gene hypermethylation coexist in ADPKD. We found that the genomic DNA of ADPKD kidney tissues showed extensive demethylation by whole-genome bisulphite sequencing, while some regional DNA methylation from body fluids, such as blood and urine, can be used as diagnostic or prognostic biomarkers to predict PKD progression. Histone modifications construct the histone code mediated by histone methyltransferases and contribute to aberrant methylation changes in PKD. Considering the complexity of methylation abnormalities occurring in different regions and genes on the PKD epigenome, more specific therapy aiming to restore to the normal genome should lead to the development of epigenetic treatment.
常染色体显性多囊肾病（ADPKD）是全球最常见的遗传性肾病，也是终末期肾病的主要病因之一。 和 是两个主要导致ADPKD发生和发展的基因。其确切机制尚未完全明确。近年来，表观遗传修饰受到越来越多的关注。染色质甲基化是多囊肾病表观遗传变化中非常重要的一类，主要涉及DNA、组蛋白和RNA甲基化。在ADPKD中，基因组低甲基化和区域基因高甲基化并存。我们通过全基因组亚硫酸氢盐测序发现，ADPKD肾组织的基因组DNA呈现广泛的去甲基化，而来自血液和尿液等体液的一些区域DNA甲基化可作为诊断或预后生物标志物来预测PKD的进展。组蛋白修饰由组蛋白甲基转移酶介导构建组蛋白密码，并导致PKD中异常的甲基化变化。考虑到PKD表观基因组不同区域和基因发生的甲基化异常的复杂性，旨在恢复正常基因组的更特异性治疗应会推动表观遗传治疗的发展。
