ADPKD的表观遗传调控、炎症和甲基化的分子机制

The Molecular Mechanisms of Epigenetic Regulation, Inflammation, and Methylation in ADPKD

常染色体显性多囊肾病(ADPKD)是一种由PKD1和PKD2基因突变引起的遗传性疾病,其特征是肾脏中多个囊肿的进行性生长,最终导致终末期肾病(ESKD),需要肾脏替代治疗。研究表明,疾病的进展是多种因素共同作用的结果。因此,了解分子机制将有助于制定ADPKD治疗的精确治疗策略。表观遗传调节、间质炎症和细胞调控死亡的作用最近成为ADPKD研究的热点。不同的表观遗传调节因子表达与囊肿进展有关的炎症标志物,在囊肿生长之前就可检测到。此外,在人类和PKD动物模型中,炎症细胞(如巨噬细胞和T细胞)的浸润与囊肿生长和肾功能恶化有关。然而,在ADPKD中,细胞死亡是否促进或延迟囊肿生长还没有达成共识。因此,有必要研究PKD基因突变、表观基因组、炎症和细胞死亡之间的交互关系,以理解为什么患者的遗传性PKD基因突变可能导致这些过程的失调,从而增加肾囊肿的进展。

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease caused by mutations in the PKD1 and PKD2 genes, characterized by the progressive growth of multiple cysts in the kidney, ultimately leading to end-stage kidney disease (ESKD) and requiring renal replacement therapy. Research has shown that the progression of diseases is the result of multiple factors working to-gether. Therefore, understanding the molecular mechanisms will help develop precise treatment strategies for ADPKD. The role of epigenetic regulation, interstitial inflammation, and cell death regulation has recently become a hot topic in ADPKD research. Inflammatory markers related to the expression of different epigenetic regulatory factors and cyst progression can be detected be-fore cyst growth. In addition, in human and PKD animal models, the infiltration of inflammatory cells (such as macrophages and T cells) is associated with cyst growth and deterioration of renal function. However, there is no consensus on whether cell death promotes or delays cyst growth in ADPKD. Therefore, it is necessary to study the interaction between PKD gene mutations, epige-nomes, inflammation, and cell death in order to understand why genetic PKD gene mutations in pa-tients may lead to dysregulation of these processes, thereby increasing the progression of renal cysts.