Suppression of hepatic stellate cell activation by microRNA-29b |
| |
Authors: | Sekiya Yumiko Ogawa Tomohiro Yoshizato Katsutoshi Ikeda Kazuo Kawada Norifumi |
| |
Institution: | aDepartment of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan;bLiver Research Center, Graduate School of Medicine, Osaka City University, Osaka, Japan;cPhoenixBio Co. Ltd., Hiroshima, Japan;dDepartment of Anatomy and Cell Biology, Graduate School of Medical Sciences, Nagoya City University, Aichi, Japan |
| |
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. |
| |
Keywords: | Abbreviations: BSA bovine serum albumin Col1a1 alpha 1 (I) collagen Col1a2 alpha 2 (I) collagen DDR discoidin domain receptor DAPI 4&prime 6-diamidino-2-phenylindole DMEM Dulbecco&rsquo s modified Eagle&rsquo s medium ECM extracellular matrix ERK extracellular signal-regulated kinase FAK focal adhesion kinase FBS fetal bovine serum FN fibronectin GAPDH glyceraldehyde-3-phosphate dehydrogenase HSC hepatic stellate cell ITGB1 integrin β1 miRNA microRNA PBS phosphate buffered saline PDGFR-β platelet-derived growth factor receptor-β PI3K phosphatidylinositol-3 kinase SDS sodium dodecyl sulfate α-SMA α-smooth muscle actin TGF-β transforming growth factor-β 3&prime UTR 3&prime untranslated region |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|