《生命科学》 2023, 35(4): 472-479
m6A修饰在肝纤维化中的研究进展
摘 要：
N6- 甲基腺苷(N6-methyladenosine, m6A) 作为真核生物中最丰富的RNA 内部修饰，影响RNA 的加工，调节mRNA 翻译效率，并与多种表观遗传学机制发生交互作用，进而在多种生理过程中调控基因的表达。肝纤维化是细胞外基质(extracellular matrix, ECM) 蛋白( 主要是Ⅰ型和Ⅲ型胶原蛋白) 积累形成的纤维瘢痕取代正常组织的过程，是肝脏对慢性损伤的病理性修复反应。m6A 修饰直接参与肝细胞损伤、炎症细胞募集和肝星状细胞激活等肝纤维化过程，并通过降低HBV 蛋白的表达、与微RNA (microRNA) 和肠道菌群相互作用等途径间接影响肝纤维化的发生发展。由于肝脏的再生能力较强，当慢性炎症或肝损伤的主要病因去除后，早期已经发生纤维化的肝脏可逆转为正常肝脏。m6A 修饰在肝纤维化中的双重作用可为平衡机体纤维化过程提供思路。该文综述了m6A 修饰在肝纤维化中的功能和作用机制，以期为相关疾病的诊疗提供新的思路。
通讯作者：杨 富 , Email:angfusq1997@smmu.edu.cn
Abstract:
N6-methyladenosine (m6A) is the most abundant RNA internal modification in eukaryotes. This
modification controls specific gene expression in various physiological processes through affecting the process of RNA, regulating the efficiency of mRNA translation and performing crosstalks with other epigenetic mechanisms. As liver fibrosis is a process in which fibrous scars formed by the accumulation of extracellular matrix (ECM) proteins (mainly collagen types I and III) replace normal tissues. This process is a pathological repair response of the liver to chronic injury. The m6A modification is directly involved in liver fibrotic processes such as hepatocyte injury, inflammatory cell recruitment, and activation of hepatic stellate cells. Moreover, it may reduce HBV protein expression, interact with microRNAs and intestinal flora to affect the development and progression of liver fibrosis indirectly. Due to the strong regenerative capacity of the liver, liver fibrosis at an early stage can be reversed to a normal liver when the primary cause of chronic inflammation or liver injury is removed. The dual roles of m6A modification in liver fibrosis may provide views for balancing the fibrotic process in the organism. This review summarizes the functions and mechanisms of m6A modification in liver fibrosis, aiming to provide new ideas for the diagnosis and treatment of related diseases.
Communication Author：YANG Fu , Email:angfusq1997@smmu.edu.cn
