title: MiR-29a Assists in Preventing the Activation of Human Stellate Cells and Promotes Recovery From Liver Fibrosis in Mice.
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.
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.|Department of Medical Nutrition, Graduate School of Human Life Science, Osaka City University, Osaka, Japan.|Current address: Department of Nutrition Management, Osaka University Medical Hospital, Osaka, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Itami
authors.affiliation: Department of Molecular Pathology, Tokyo Medical University, Tokyo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kuroda
authors.affiliation: Phoenixbio Co. Ltd, Hiroshima, Japan.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Yoshizato
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Murakami
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000009:adverse effects*; D002460:Cell Line; D002470:Cell Survival; D003094:Collagen / Q000008:administration & dosage / Q000737:chemistry*; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000235:genetics / Q000628:therapy*; D008222:Lymphokines / Q000235:genetics; D051379:Mice; D035683:MicroRNAs / Q000008:administration & dosage* / Q000737:chemistry; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D013853:Thioacetamide / Q000009:adverse effects*
chemical_list: C000716127:COL1A1 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D008222:Lymphokines; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D010982:Platelet-Derived Growth Factor; C059821:atelocollagen; C411423:platelet-derived growth factor C; D013853:Thioacetamide; D003094:Collagen; D002251:Carbon Tetrachloride