Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.
Int J Mol Sci. 2021 Jul 29;22(15):8139. doi: 10.3390/ijms22158139.
Remarkable progress has been made in the treatment and control of hepatitis B and C viral infections. However, fundamental treatments for diseases in which liver fibrosis is a key factor, such as cirrhosis, alcoholic/nonalcoholic steatohepatitis, autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis, are still under development and remain an unmet medical need. To solve this problem, it is essential to elucidate the pathogenesis of liver fibrosis in detail from a molecular and cellular perspective and to develop targeted therapeutic agents based on this information. Recently, microRNAs (miRNAs), functional RNAs of 22 nucleotides, have been shown to be involved in the pathogenesis of liver fibrosis. In addition, extracellular vesicles called "exosomes" have been attracting attention, and research is being conducted to establish noninvasive and extremely sensitive biomarkers using miRNAs in exosomes. In this review, we summarize miRNAs directly involved in liver fibrosis, miRNAs associated with diseases leading to liver fibrosis, and miRNAs related to complications of cirrhosis. We will also discuss the efficacy of each miRNA as a biomarker of liver fibrosis and pathology, and its potential application as a therapeutic agent.
在乙型和丙型肝炎病毒感染的治疗和控制方面已经取得了显著进展。然而,对于以肝纤维化为关键因素的疾病,如肝硬化、酒精性/非酒精性脂肪性肝炎、自身免疫性肝炎、原发性胆汁性胆管炎和原发性硬化性胆管炎,基本治疗仍在开发中,仍然是未满足的医疗需求。为了解决这个问题,必须从分子和细胞的角度详细阐明肝纤维化的发病机制,并在此基础上开发靶向治疗药物。最近,microRNAs(miRNAs),即 22 个核苷酸的功能性 RNA,已被证明与肝纤维化的发病机制有关。此外,被称为“外泌体”的细胞外囊泡也引起了人们的关注,正在研究利用外泌体中的 miRNAs 建立非侵入性和极其敏感的生物标志物。在这篇综述中,我们总结了直接参与肝纤维化的 miRNAs、与导致肝纤维化的疾病相关的 miRNAs 以及与肝硬化并发症相关的 miRNAs。我们还将讨论每种 miRNA 作为肝纤维化和病理学生物标志物的功效及其作为治疗剂的潜在应用。