Suppression of hepatic stellate cell activation by microRNA-29b
Suppression of hepatic stellate cell activation by microRNA-29b
复制标题
DOI：
10.1016/j.bbrc.2011.07.041
复制
发表时间：
2011-08-19
影响因子：
3.1
通讯作者：
Kawada, Norifumi
中科院分区：
文献类型：
--
作者：
Sekiya, Yumiko;Ogawa, Tomohiro;Kawada, Norifumi
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 FDGFR-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. (C) 2011 Elsevier Inc. All rights reserved.
