Mechanism and Therapeutic Opportunities of Histone Modifications in Chronic Liver Disease.
Mechanism and Therapeutic Opportunities of Histone Modifications in Chronic Liver Disease.
复制标题
组蛋白修饰在慢性肝病中的机制和治疗机会
DOI：
10.3389/fphar.2021.784591
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发表时间：
2021
影响因子：
5.6
通讯作者：
Gao J
中科院分区：
文献类型：
--
作者：
Cai Q;Gan C;Tang C;Wu H;Gao J
慢性肝病（CLD）是一个全球性的健康问题，造成了沉重的残疾负担和医疗保健利用率的增加。表观基因组改变在CLD的发生和进展中发挥重要作用。组蛋白修饰，包括乙酰化、甲基化和磷酸化，是影响基因转录活性的表观遗传修饰的重要组成部分。与基因突变不同，组蛋白修饰是可塑且可逆的。它们可以在不改变 DNA 序列的情况下进行药理学调节。因此，可能有机会通过针对组蛋白修饰来逆转 CLD 来建立干预解决方案。在这里，我们总结了组蛋白修饰在酒精性肝病 (ALD)、代谢相关脂肪性肝病 (MAFLD)、病毒性肝炎、自身免疫性肝病、药物性肝损伤 (DILI) 和肝纤维化或肝硬化中的作用。还研究了组蛋白修饰转化为治疗药物的潜在靶点。展望未来，需要选择性靶向组蛋白修饰的高效、低毒药物来彻底逆转慢性肝病并预防肝硬化和恶性肿瘤的发展。
Chronic liver disease (CLD) represents a global health problem, accounting for the heavy burden of disability and increased health care utilization. Epigenome alterations play an important role in the occurrence and progression of CLD. Histone modifications, which include acetylation, methylation, and phosphorylation, represent an essential part of epigenetic modifications that affect the transcriptional activity of genes. Different from genetic mutations, histone modifications are plastic and reversible. They can be modulated pharmacologically without changing the DNA sequence. Thus, there might be chances to establish interventional solutions by targeting histone modifications to reverse CLD. Here we summarized the roles of histone modifications in the context of alcoholic liver disease (ALD), metabolic associated fatty liver disease (MAFLD), viral hepatitis, autoimmune liver disease, drug-induced liver injury (DILI), and liver fibrosis or cirrhosis. The potential targets of histone modifications for translation into therapeutics were also investigated. In prospect, high efficacy and low toxicity drugs that are selectively targeting histone modifications are required to completely reverse CLD and prevent the development of liver cirrhosis and malignancy.
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DOI：
10.1038/s41575-020-00406-0
发表时间：
2021-03
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
Abdelmalek MF
通讯作者：
Abdelmalek MF
影响因子：
16.6
作者：
Bricambert J;Alves-Guerra MC;Esteves P;Prip-Buus C;Bertrand-Michel J;Guillou H;Chang CJ;Vander Wal MN;Canonne-Hergaux F;Mathurin P;Raverdy V;Pattou F;Girard J;Postic C;Dentin R
通讯作者：
Dentin R
影响因子：
64.8
作者：
ALLAN, J;HARTMAN, PG;AVILES, FX
通讯作者：
AVILES, FX
影响因子：
3.6
作者：
Bardag-Gorce, F.;Li, J.;Oliva, J.;Lu, S. C.;French, B. A.;French, S. W.
通讯作者：
French, S. W.
影响因子：
8.8
作者：
Becares, Natalia;Gage, Matthew C.;Pineda-Torra, Ines
通讯作者：
Pineda-Torra, Ines