Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
Biochem Biophys Res Commun. 2010 Jan 1;391(1):316-21. doi: 10.1016/j.bbrc.2009.11.056. Epub 2009 Nov 12.
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression through imperfect base pairing with the 3' untranslated region (3'UTR) of target mRNA. We studied the regulation of alpha 1 (I) collagen (Col1A1) expression by miRNAs in human stellate cells, which are involved in liver fibrogenesis. Among miR-29b, -143, and -218, whose expressions were altered in response to transforming growth factor-beta1 or interferon-alpha stimulation, miR-29b was the most effective suppressor of type I collagen at the mRNA and protein level via its direct binding to Col1A1 3'UTR. miR-29b also had an effect on SP1 expression. These results suggested that miR-29b is involved in the regulation of type I collagen expression by interferon-alpha in hepatic stellate cells. It is anticipated that miR-29b will be used for the regulation of stellate cell activation and lead to antifibrotic therapy.
微小 RNA(miRNAs)是通过与靶 mRNA 的 3'非翻译区(3'UTR)的不完全碱基配对来调节基因表达的小非编码 RNA。我们研究了 miRNA 对参与肝纤维化的人星状细胞中 alpha 1(I)胶原(Col1A1)表达的调节。在 miR-29b、-143 和 -218 中,其表达在转化生长因子-β1 或干扰素-α刺激下发生改变,miR-29b 通过直接与其 Col1A1 3'UTR 结合,是对 I 型胶原在 mRNA 和蛋白水平上最有效的抑制物。miR-29b 对 SP1 表达也有影响。这些结果表明,miR-29b 参与了干扰素-α在肝星状细胞中对 I 型胶原表达的调节。预计 miR-29b 将用于调节星状细胞的激活,并导致抗纤维化治疗。