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Mol Ther. 2016 Oct;24(10):1848-1859. doi: 10.1038/mt.2016.127. Epub 2016 Jun 23.

MiR-29a Assists in Preventing the Activation of Human Stellate Cells and Promotes Recovery From Liver Fibrosis in Mice.

Author information

1
Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
2
Department of Medical Nutrition, Graduate School of Human Life Science, Osaka City University, Osaka, Japan.
3
Current address: Department of Nutrition Management, Osaka University Medical Hospital, Osaka, Japan.
4
Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.
5
Phoenixbio Co. Ltd, Hiroshima, Japan.

Abstract

The microRNA-29 (miR-29) family is known to suppress the activation of hepatic stellate cells (HSCs) and reversibly control liver fibrosis; however, the mechanism of how miR-29a controls liver fibrosis remains largely unknown. This study was conducted to clarify the mechanism of anti-fibrotic effect of miR-29a and to explore if miR-29a is a promising candidate for nucleic acid medicine against liver fibrosis. Two liver fibrosis murine models (carbon tetrachloride or thioacetamide) were used. MiR-29a mixed with atelocollagen was systemically administered. Hepatic fibrosis was evaluated by histological analysis and the expression levels of fibrosis-related genes. We observed that miR-29a treatment dramatically accelerated the reversion of liver fibrosis in vivo. Additionally, miR-29a regulated the mRNA expression of collagen type I alpha 1 (COL1A1) and platelet-derived growth factor C (PDGFC). We also noted that miR-29a significantly suppressed COL1A1 mRNA expression and cell viability and significantly increased caspase-9 activity (P < 0.05) in LX-2 cells. Pretreatment of miR-29a inhibited activation of LX-2 cell by transforming growth factor beta treatment. MiR-29a exhibited anti-fibrotic effect without cell toxicity in vivo and directly suppressed the expression of PDGF-related genes as well as COL1A1 and induced apoptosis of LX-2 cells. MiR-29a is a promising nucleic acid inhibitor to target liver fibrosis.

PMID:
27480597
PMCID:
PMC5112039
DOI:
10.1038/mt.2016.127
[Indexed for MEDLINE]
Free PMC Article

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