Suppression of hepatic stellate cell activation by microRNA-29b
| Autor: | Norifumi Kawada, Katsutoshi Yoshizato, Kazuo Ikeda, Tomohiro Ogawa, Yumiko Sekiya |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Liver Cirrhosis
Male MAPK/ERK pathway Biophysics Biology Cell morphology Biochemistry Collagen Type I Receptor Platelet-Derived Growth Factor beta Mice microRNA Hepatic Stellate Cells Animals RNA Messenger Discoidin Domain Receptors Molecular Biology Protein kinase B Regulation of gene expression Cell growth Integrin beta1 Receptor Protein-Tyrosine Kinases Cell Biology Molecular biology Hepatic stellate cell activation Actins Fibronectins Cell biology Collagen Type I alpha 1 Chain Mice Inbred C57BL MicroRNAs Receptors Mitogen Hepatic stellate cell |
| Zdroj: | Biochemical and Biophysical Research Communications. 412:74-79 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2011.07.041 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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