title: Upregulation of microRNA-126 in hepatic stellate cells may affect pathogenesis of liver fibrosis through the NF-κB pathway.
abstract: Hepatic fibrosis, which results from chronic liver disease, currently lacks effective treatment. MicroRNAs, a group of small noncoding RNA molecules, have been observed to play an essential role in liver diseases, including hepatic fibrosis. In this study, we described the regulation of nuclear factor kappa B (NF-κB) inhibitor alpha (IκBα) and its possible signaling pathway by miR-126 in human hepatic stellate cell (HSC) line LX-2. The 3'-untranslated region (3'-UTR) of IκBα combined with miR-126 was analyzed by using a dual-luciferase reporter assay. Furthermore, the effects of miR-126 on IκBα mRNA and protein and NF-κB protein expression were assessed by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and western blot analysis in the human HSC LX-2 cell line transfected with miR-126 mimic or inhibitor. Moreover, to understand the molecular mechanism of miR-126 in promoting liver fibrosis through NF-κB signaling pathway, the NF-κB downstream signaling factors expression such as transforming growth factor (TGF)-β1 and collagen I mRNA were detected by real-time qRT-PCR. We identified that IκBα is a potential target gene of miR-126, by directly targeting its 3'-UTR. Endogenous miR-126 and exogenous miR-126 mimic inhibited IκBα expression. Moreover, overexpression of miR-126 reduced total and the cytoplasm IκBα protein expression and increased total and cytoblast NF-κB protein expression of LX-2. Conversely, knockdown of miR-126 could inhibit NF-κB activation by upregulation of IκBα protein expression. Further, miR-126 promoted TNF-a-induced TGF-β1 and collagen I mRNA expression in LX-2 cells. miR-126 may play an important role in hepatic fibrosis by downregulating the expression of IκBα partly through the NF-κB signaling pathway.
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College , Zhanjiang, China .
authors.forename: Xiao
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College , Zhanjiang, China .
authors.forename: Wenkai
authors.initials: W
authors.lastname: Tan
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College , Zhanjiang, China .
authors.forename: Si
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College , Zhanjiang, China .
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College , Zhanjiang, China .
authors.forename: Shicai
authors.initials: S
authors.lastname: Ye
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College , Zhanjiang, China .
authors.forename: Caiyuan
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College , Zhanjiang, China .
authors.forename: Yanting
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College , Zhanjiang, China .
authors.forename: Juncheng
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College , Zhanjiang, China .
authors.forename: Junwei
authors.initials: J
authors.lastname: Cen
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College , Zhanjiang, China .
authors.forename: Juxiang
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College , Zhanjiang, China .
authors.forename: Rong
authors.initials: R
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, The Affiliated Hospital of Guangdong Medical College , Zhanjiang, China .
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D020413:3' Untranslated Regions; D024042:Collagen Type I; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1