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DNA甲基化及其抑制剂在肝纤维化中的作用和机制

Role and mechanism of DNA methylation and its inhibitors in hepatic fibrosis.

作者信息

Lyu Shi-Yi, Xiao Wang, Cui Guang-Zu, Yu Cheng, Liu Huan, Lyu Min, Kuang Qian-Ya, Xiao En-Hua, Luo Yong-Heng

机构信息

Department of Radiology, The Second Xiangya Hospital, Central-South University, Changsha, Hunan, China.

Department of Gastrointestinal Surgery, The Second Xiangya Hospital, Central-South University, Changsha, Hunan, China.

出版信息

Front Genet. 2023 Mar 28;14:1124330. doi: 10.3389/fgene.2023.1124330. eCollection 2023.

Abstract

Liver fibrosis is a repair response to injury caused by various chronic stimuli that continually act on the liver. Among them, the activation of hepatic stellate cells (HSCs) and their transformation into a myofibroblast phenotype is a key event leading to liver fibrosis, however the mechanism has not yet been elucidated. The molecular basis of HSC activation involves changes in the regulation of gene expression without changes in the genome sequence, namely, epigenetic regulation. DNA methylation is a key focus of epigenetic research, as it affects the expression of fibrosis-related, metabolism-related, and tumor suppressor genes. Increasing studies have shown that DNA methylation is closely related to several physiological and pathological processes including HSC activation and liver fibrosis. This review aimed to discuss the mechanism of DNA methylation in the pathogenesis of liver fibrosis, explore DNA methylation inhibitors as potential therapies for liver fibrosis, and provide new insights on the prevention and clinical treatment of liver fibrosis.

摘要

肝纤维化是肝脏对各种持续作用于肝脏的慢性刺激所导致损伤的一种修复反应。其中,肝星状细胞(HSCs)的激活及其向肌成纤维细胞表型的转变是导致肝纤维化的关键事件,但其机制尚未阐明。肝星状细胞激活的分子基础涉及基因表达调控的变化,而基因组序列不变,即表观遗传调控。DNA甲基化是表观遗传学研究的一个关键焦点,因为它影响纤维化相关、代谢相关和肿瘤抑制基因的表达。越来越多的研究表明,DNA甲基化与包括肝星状细胞激活和肝纤维化在内的多种生理和病理过程密切相关。本综述旨在探讨DNA甲基化在肝纤维化发病机制中的作用机制,探索DNA甲基化抑制剂作为肝纤维化潜在治疗方法的可能性,并为肝纤维化的预防和临床治疗提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f1d/10086238/c5c0fecfeb60/fgene-14-1124330-g001.jpg

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