Molecular Mechanisms of Epigenetic Regulation, Inflammation, and Cell Death in ADPKD.
Molecular Mechanisms of Epigenetic Regulation, Inflammation, and Cell Death in ADPKD.
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DOI：
10.3389/fmolb.2022.922428
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发表时间：
2022
影响因子：
5
通讯作者：
中科院分区：
文献类型：
--
作者：
常染色体显性多囊肾病（ADPKD）是一种遗传性疾病，由PKD1和PKD2基因突变引起，以肾脏内多个囊肿的进行性生长为特征，最终导致终末期肾病（ESKD），需要肾脏替代治疗。此外，研究表明，疾病的进展是多种因素共同作用的结果。因此，了解分子机制应该有助于制定精确的治疗策略来治疗ADPKD。表观遗传调节、间质炎症和调节细胞死亡的作用最近成为ADPKD的焦点。不同的表观遗传调节因子，以及甚至在囊肿生长之前就可检测到的炎症标志物的存在，与囊肿的进展有关。此外，在人类和PKD动物模型中，巨噬细胞和T细胞等炎症细胞的浸润与囊肿生长和肾功能恶化有关。有证据支持PKD基因突变在ADPKD的表观遗传机制和炎症反应调控中的直接作用。此外，调控细胞死亡（包括凋亡、自噬和铁下垂）在ADPKD中的作用已被研究。然而，细胞死亡是否促进或延迟ADPKD的囊肿生长尚无共识。因此，有必要建立PKD基因突变、表观基因组、炎症和细胞死亡之间的相互作用图，以了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，从而增加肾囊肿形成的进展。
Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder, which is caused by mutations in the PKD1 and PKD2 genes, characterizing by progressive growth of multiple cysts in the kidneys, eventually leading to end-stage kidney disease (ESKD) and requiring renal replacement therapy. In addition, studies indicate that disease progression is as a result of a combination of factors. Understanding the molecular mechanisms, therefore, should facilitate the development of precise therapeutic strategies for ADPKD treatment. The roles of epigenetic modulation, interstitial inflammation, and regulated cell death have recently become the focuses in ADPKD. Different epigenetic regulators, and the presence of inflammatory markers detectable even before cyst growth, have been linked to cyst progression. Moreover, the infiltration of inflammatory cells, such as macrophages and T cells, have been associated with cyst growth and deteriorating renal function in humans and PKD animal models. There is evidence supporting a direct role of the PKD gene mutations to the regulation of epigenetic mechanisms and inflammatory response in ADPKD. In addition, the role of regulated cell death, including apoptosis, autophagy and ferroptosis, have been investigated in ADPKD. However, there is no consensus whether cell death promotes or delays cyst growth in ADPKD. It is therefore necessary to develop an interactive picture between PKD gene mutations, the epigenome, inflammation, and cell death to understand why inherited PKD gene mutations in patients may result in the dysregulation of these processes that increase the progression of renal cyst formation.
影响因子：
3.7
作者：
Liu Y;Käch A;Ziegler U;Ong AC;Wallace DP;Arcaro A;Serra AL
通讯作者：
Serra AL