Upregulation of microRNA-126 in hepatic stellate cells may affect pathogenesis of liver fibrosis through the NF-κB pathway.

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)-ß1 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-ß1 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.

An adenosine A3 receptor agonist inhibits DSS-induced colitis in mice through modulation of the NF-κB signaling pathway.

The role of the adenosine A3 receptor (A3AR) in experimental colitis is controversial. The A3AR agonist N(6)-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA) has been shown to have a clinical benefit, although studies in A3AR-deficient mice suggest a pro-inflammatory role. However, there are no studies on the effect of 2-Cl-IB-MECA and the molecular mechanism of action of A3AR in murine colitis models in vivo. Is it the same as that observed in vitro? The interaction between 2-CL-IB-MECA and A3AR in a murine colitis model and the signaling pathways associated with this interaction remain unclear. Here we demonstrate a role for the NF-κB signaling pathway and its effect on modifying the activity of proinflammatory factors in A3AR-mediated biological processes. Our results demonstrated that A3AR activation possessed marked effects on experimental colitis through the NF-κB signaling pathway.