Suppression of hepatic stellate cell activation by microRNA-29b

Journal Article · Fri Aug 19 04:00:00 EDT 2011 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2011.07.041· OSTI ID:22207456

Sekiya, Yumiko; Ogawa, Tomohiro ^[1]; Yoshizato, Katsutoshi ^[1]; Ikeda, Kazuo ^[2]; Kawada, Norifumi ^[1]

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1. Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka (Japan)
2. Department of Anatomy and Cell Biology, Graduate School of Medical Sciences, Nagoya City University, Aichi (Japan)

Highlights: {yields} Expression of miR-29b was found to be down-regulated during the activation of hepatic stellate cells in primary culture. {yields} Transfection of a miR-29b precursor markedly attenuated the expression of Col1a1 and Col1a2 mRNAs. {yields} It blunted the increased expression of {alpha}-SMA, DDR2, FN1, ITGB1, and PDGFR-b mRNAs essential for stellate cell activation. {yields} miR-29b overexpression led stellate cells to remain in a quiescent state, as evidenced by their star-like morphology. {yields} miR-29b overexpression suppressed the expression of c-fos mRNA. -- 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 {alpha}-SMA, DDR2, FN1, ITGB1, and PDGFR-{beta}, 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.

• OSTI ID: 22207456
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 412; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ACTIN
ALBUMINS
CATTLE
CELL PROLIFERATION
COLLAGEN
FIBROSIS
GENE REGULATION
GROWTH FACTORS
INHIBITION
LIVER
MESSENGER-RNA
MICE
MORPHOLOGY
MUSCLES
PHOSPHATES
PHOSPHORYLATION
RECEPTORS
SODIUM
SULFATES