Diagnosis and Therapeutic Management of Liver Fibrosis by MicroRNA

Abstract

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.

Keywords: exosomal miRNA; liver cirrhosis; liver fibrosis; microRNA.

Figure 1

Schematic diagram of the relationship between miRNAs and liver fibrosis. HSCs are activated in livers damaged by viruses, alcohol, lipid accumulation, and autoimmunity. Various miRNAs are involved in this process and affect molecules such as TGF-β, NF-κB, and PTEN, which are involved in different pathways. This can improve inflammation or, conversely, result in ECM accumulation and cirrhosis. HSC: hepatic stellate cell; TGF-β: transforming growth factor-β; NF-κB: nuclear factor-kappa B; PTEN: phosphatase and tensin homolog; MFB: myofibroblast; ECM: extracellular matrix; miRNA: micro ribonucleic acid; HBV: hepatitis B virus; HCV: hepatitis C virus.