内源性逆转录病毒
生物
表观遗传学
肾
DNA甲基化
减压
免疫系统
先天免疫系统
逆转录酶
免疫学
遗传学
核糖核酸
基因
基因表达
基因组
心理压抑
作者
Poonam Dhillon,Kelly A. Mulholland,Hailong Hu,Jihwan Park,Xin Sheng,Amin Abedini,Hongbo Liu,Allison Vassalotti,Junnan Wu,Katalin Suszták
标识
DOI:10.1038/s41467-023-36212-w
摘要
Inflammation is a common feature of all forms of chronic kidney disease; however, the underlying mechanism remains poorly understood. Evolutionarily inherited endogenous retroviruses (ERVs) have the potential to trigger an immune reaction. Comprehensive RNA-sequencing of control and diseased kidneys from human and mouse disease models indicated higher expression of transposable elements (TEs) and ERVs in diseased kidneys. Loss of cytosine methylation causing epigenetic derepression likely contributes to an increase in ERV levels. Genetic deletion/pharmacological inhibition of DNA methyltransferase 1 (DNMT1) induces ERV expression. In cultured kidney tubule cells, ERVs elicit the activation of cytosolic nucleotide sensors such as RIG-I, MDA5, and STING. ERVs expressions in kidney tubules trigger RIG-I/STING, and cytokine expression, and correlate with the presence of immune cells. Genetic deletion of RIG-I or STING or treatment with reverse transcriptase inhibitor ameliorates kidney fibroinflammation. Our data indicate an important role of epigenetic derepression-induced ERV activation triggering renal fibroinflammation.
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