title: Suppression of hepatic stellate cell activation by microRNA-29b.
abstract: MicroRNAs (miRNAs) participate in the regulation of cellular functions including proliferation, apoptosis, and migration. It has been previously shown that the miR-29 family is involved in regulating type I collagen expression by interacting with the 3'UTR of its mRNA. Here, we investigated the roles of miR-29b in the activation of mouse primary-cultured hepatic stellate cells (HSCs), a principal collagen-producing cell in the liver. Expression of miR-29b was found to be down-regulated during HSC activation in primary culture. Transfection of a miR-29b precursor markedly attenuated the expression of Col1a1 and Col1a2 mRNAs and additionally blunted the increased expression of α-SMA, DDR2, FN1, ITGB1, and PDGFR-β, which are key genes involved in the activation of HSCs. Further, overexpression of miR-29b led HSCs to remain in a quiescent state, as evidenced by their quiescent star-like cell morphology. Although phosphorylation of FAK, ERK, and Akt, and the mRNA expression of c-jun was unaffected, miR-29b overexpression suppressed the expression of c-fos mRNA. These results suggested that miR-29b is involved in the activation of HSCs and could be a candidate molecule for suppressing their activation and consequent liver fibrosis.
authors.affiliation: Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Sekiya
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Ogawa
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Yoshizato
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ikeda
authors.forename: Norifumi
authors.initials: N
authors.lastname: Kawada
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D000070818:Discoidin Domain Receptors; D005353:Fibronectins / Q000235:genetics; D055166:Hepatic Stellate Cells / Q000378:metabolism* / Q000473:pathology*; D019012:Integrin beta1 / Q000235:genetics; D008103:Liver Cirrhosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics; D011975:Receptors, Mitogen / Q000235:genetics
chemical_list: C558396:Acta2 protein, mouse; D000199:Actins; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D005353:Fibronectins; D019012:Integrin beta1; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; D011975:Receptors, Mitogen; D000070818:Discoidin Domain Receptors; D020794:Receptor Protein-Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta