Hepatic Stellate Cells and microRNAs in Pathogenesis of Liver Fibrosis

Abstract

microRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by either blocking translation or inducing degradation of target mRNA. miRNAs play essential roles in diverse biological and pathological processes, including development of hepatic fibrosis. Hepatic stellate cells (HSCs) play a central role in development of hepatic fibrosis and there are intricate regulatory effects of miRNAs on their activation, proliferation, collagen production, migration, and apoptosis. There are multiple differentially expressed miRNAs in activated HSCs, and in this review we aim to summarize current data on miRNAs that participate in the development of hepatic fibrosis. Based on this review, miRNAs may serve as biomarkers for diagnosis of liver disease, as well as markers of disease progression. Most importantly, dysregulated miRNAs may potentially be targeted by novel therapies to treat and reverse progression of hepatic fibrosis.

Differential miRNA Expression in the Liver of Balb/c Mice Protected by Vaccination during Crisis of Plasmodium chabaudi Blood-Stage Malaria

“…Similar courses of miRNA expression levels are here found for miR-30a known to be involved in manifestation and resolution of liver fibrosis (Roy et al, 2015), for miR-27a described to be involved in fibrosis (Cui et al, 2016), and for mir-29b known to suppress transcription of genes encoding for extracellular matrix proteins (cf. Table 1) (Roderburg et al, 2011; Lambrecht et al, 2015; Kitano and Bloomston, 2016). Thus, the dys-regulations of these different miRNA species may presumably due to the liver injuries induced by P. chabaudi blood-stage malaria occurring during precrisis in both vaccination-protected and non-vaccinated mice.…”

Hepatic stellate cells as key target in liver fibrosis

“…High-throughput miRNA profiling and other technologies have identified pro-fibrogenic miRNAs over-expressed in activated HSCs, including miR-9a-5p, miR-17-5p, miR-21, miR-27, miR-31, miR-33a, miR-34a/c, miR-125, miR-126, miR-130a/b, miR-181b, miR-214-5p, miR-195, miR-199a/b, miR-221, and miR-222, each of which induces proliferation, collagen secretion, and/or migration via a variety of pathways, and anti-fibrotic miRNAs, including miR-16, miR-19b, miR-29, miR-30, miR-101, miR-122, miR-133a, miR-144, miR-146a, miR-150, miR-155, miR-192, miR-195, miR-335, miR-454, and miR-483, although direction of change could depend on biological and/or experimental contexts [267–269]. miR-378 was recently shown to limit HSC activation by suppressing Gli3 [270].…”

Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets

“…Liver fibrosis is a complex process that results from various forms of chronic hepatic disease and is associated with excess hepatocellular death[2,12,13]. The main etiologies of liver fibrosis are schistosome and chronic viral hepatitis infection, nonalcoholic fatty liver disease (NAFLD), alcoholic liver disease (ALD), and cholestatic and autoimmune liver disease[1,14-17].…”

“…Upon fibrogenic initiation, qHSCs differentiate into aHSCs, upon which they lose the intracellular lipid droplets and acquire a myofibroblastic phenotype characterized by marked upregulation of a-smooth muscle actin (a-SMA, ACTA2), desmin (DES), and type I collagen (COL1A1)[8-10]. The sustained buildup of collagens distorts the liver parenchyma and vascular architecture, resulting in impaired liver function, scar deposition, and liver fibrosis[1,2,12,14,17]. The initiation, progression, and resolution of liver fibrosis involving HSCs are present in Figure 1.…”