MiR‐195‐3p alleviates homocysteine‐mediated atherosclerosis by targeting IL‐31 through its epigenetics modifications. Issue 10 (30th September 2021)

• Record Type: Journal Article
• Authors: Xiong, Jiantuan; Ma, Fang; Ding, Ning; Xu, Lingbo; Ma, Shengchao; Yang, Anning; Hao, Yinju; Zhang, Huiping; Jiang, Yideng
• Is Part Of: Aging cell. Volume 20:Issue 10(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-09-30
• Subjects: DNA methylation -- H3K9 acetylation -- homocysteine -- inflammation -- miR‐195‐3p; Cells -- Aging -- Periodicals; 571.8783605
• DOI: 10.1111/acel.13485
• Languages: English
• ISSNs: 1474-9718

Abstract

Abstract: Atherosclerosis is a serious age‐related disease, which has a tremendous impact on health care globally. Macrophage inflammation is crucial for the initiation and progression of atherosclerosis, and microRNAs (miRNAs) recently have emerged as potent modulators of inflammation, while the underlying mechanisms of its involvement in homocysteine (Hcy)‐mediated macrophage inflammation of atherosclerosis remain largely unknown. Here, we demonstrated that elevated Hcy inhibits the expression of miR‐195‐3p, which in turn enhances IL‐31 expression and thereby causes the secretion of macrophages pro‐inflammatory factors IL‐1β, IL‐6 and TNF‐α and accelerate atherosclerosis. Furthermore, we identified that Hcy can induce DNA hypermethylation and H3K9 deacetylation of miR‐195‐3p promoter due to the increased the binding of DNMT3a and HDAC11 at its promoter. More importantly, Sp1 interacts with DNMT3a suppressed the binding of HDAC11 at miR‐195‐3p promoter and promoted its transcription. In summary, our results revealed a novel mechanism that transcriptional and epigenetic regulation of miR‐195‐3p inhibits macrophage inflammation through targeting IL‐31, which provides a candidate diagnostic marker and novel therapeutic target in cardiovascular diseases induced by Hcy. Abstract : Proposed regulation model of miR‐195‐3p expression in Hcy‐induced macrophage inflammation during the formation of atherosclerotic plaque. Downregulation of miR‐195‐3p accelerated Hcy‐induced pro‐inflammation factor expression in macrophage and formation of plaques in ApoE −/− mice by targeting IL‐31, DNMT3a and HDAC11 are responsible for the downregulation of miR‐195‐3p, and Sp1 interacts with DNMT3a was essential for HDAC11 to bind to miR‐195‐3p promoter.