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miR-30c and miR-193 are a part of the TGF-β-dependent regulatory network controlling extracellular matrix genes in liver fibrosis.

Abstract：

OBJECTIVE:MicroRNAs (miRNAs) have recently emerged as novel regulators in liver fibrosis. miR-30c and miR-193 are involved in fibrotic remodeling processes and cancer development, respectively. This study aimed to explore the role of miR-30c and miR-193 in liver fibrosis. METHODS:The regulation of miRNAs in carbon tetrachloride-induced liver fibrosis was analyzed by microarray. Expression patterns of miR-193 and miR-30c were further confirmed in fibrotic liver samples obtained from two murine models of hepatic fibrosis and human tissues. On a functional level, miRNA levels were analyzed in the context of transforming growth factor (TGF-β) mediated activation of hepatic stellate cells (HSCs). Finally, predicted targets were assessed for their roles in fibrosis by transfecting murine HSCs with miRNA mimics. RESULTS:Microarray analysis in murine fibrotic livers revealed a panel of 44 dysregulated miRNAs. In addition to previously established miRNAs known to be regulated in liver fibrosis in a TGF-β-dependent manner (e.g., miR-29, miR-133), miR-193 and miR-30c were observed to be specifically downregulated not only in experimental hepatofibrogenesis but also in human liver fibrosis, while they showed a reciprocal expression pattern after recovery from liver fibrosis. Functional experiments confirmed the TGF-β-dependent downregulation of these respective new miRNAs in HSCs. Finally, we identified TGF-β2 and SNAIL1, important regulators of extracellular matrix, as potential target genes of miR-193 and miR-30 in liver fibrosis. CONCLUSION:These results suggest that miR-30 and miR-193 are members of a network of miRNAs modifying the TGF-β-dependent regulation of extracellular matrix-related genes in HSCs in the manifestation and resolution of liver fibrosis.

journal_name

J Dig Dis

journal_title

Journal of digestive diseases

authors

Roy S,Benz F,Vargas Cardenas D,Vucur M,Gautheron J,Schneider A,Hellerbrand C,Pottier N,Alder J,Tacke F,Trautwein C,Roderburg C,Luedde T

doi

10.1111/1751-2980.12266

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

513-24

issue

eissn

1751-2972

issn

1751-2980

journal_volume

pub_type

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miR-30c and miR-193 are a part of the TGF-β-dependent regulatory network controlling extracellular matrix genes in liver fibrosis.