Membrane-bound O-acyltransferase 7 (MBOAT7)-driven phosphatidylinositol remodeling in advanced liver disease.
Membrane-bound O-acyltransferase 7 (MBOAT7)-driven phosphatidylinositol remodeling in advanced liver disease.
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晚期肝病中膜结合o -酰基转移酶7 （MBOAT7）驱动的磷脂酰肌醇重塑
DOI：
10.1016/j.jlr.2022.100234
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发表时间：
2022-07
影响因子：
6.5
通讯作者：
Brown, J. Mark
中科院分区：
文献类型：
--
作者：
Varadharajan, Venkateshwari;Massey, William J.;Brown, J. Mark
全世界每年约有200万人死于晚期肝病。大约一半的肝病相关死亡是由肝硬化并发症引起的，另一半是由病毒性肝炎和肝细胞癌引起的。不幸的是，治疗晚期肝病受试者的治疗策略的开发受到缺乏对肝病进展的机制理解和缺乏人类相关动物模型的阻碍。在过去的几年中取得了一个重要的进展，因为一些全基因组关联研究发现，编码膜结合O-酰基转移酶7（MBOAT 7）的基因附近的SNP与严重的肝脏疾病有关。这种常见的MBOAT 7变异体（rs641738，C>T）降低了MBOAT 7的表达，增加了慢性病毒性肝炎患者对非酒精性脂肪肝、酒精相关性肝病和肝纤维化的易感性。最近在小鼠中的研究还表明，Mboat 7功能丧失可以促进肝脏脂肪变性，炎症和纤维化，将这种磷脂酰肌醇重塑酶与啮齿动物和人类的肝脏健康联系起来。在此，我们回顾了最近对MBOAT 7驱动的磷脂酰肌醇重塑影响肝脏疾病进展的机制的见解，并讨论了该领域的快速进展如何为未来的药物发现提供信息。
Advanced liver diseases account for approximately 2 million deaths annually worldwide. Roughly, half of liver disease-associated deaths arise from complications of cirrhosis and the other half driven by viral hepatitis and hepatocellular carcinoma. Unfortunately, the development of therapeutic strategies to treat subjects with advanced liver disease has been hampered by a lack of mechanistic understanding of liver disease progression and a lack of human-relevant animal models. An important advance has been made within the past several years, as several genome-wide association studies have discovered that an SNP near the gene encoding membrane-bound O-acyltransferase 7 (MBOAT7) is associated with severe liver diseases. This common MBOAT7 variant (rs641738, C>T), which reduces MBOAT7 expression, confers increased susceptibility to nonalcoholic fatty liver disease, alcohol-associated liver disease, and liver fibrosis in patients chronically infected with viral hepatitis. Recent studies in mice also show that Mboat7 loss of function can promote hepatic steatosis, inflammation, and fibrosis, causally linking this phosphatidylinositol remodeling enzyme to liver health in both rodents and humans. Herein, we review recent insights into the mechanisms by which MBOAT7-driven phosphatidylinositol remodeling influences liver disease progression and discuss how rapid progress in this area could inform drug discovery moving forward.
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影响因子：
3.1
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