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Liver Receptor Homolog 1 Is a Negative Regulator of the Hepatic Acute-Phase Response

机译:肝受体同源物1是肝急性期反应的负调节剂。

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The orphan nuclear receptor liver receptor homolog 1 (LRH-1) has been reported to play an important role in bile acid biosynthesis and reverse cholesterol transport. Here, we show that LRH-1 is a key player in the control of the hepatic acute-phase response. Ectopic expression of LRH-1 with adenovirus resulted in strong inhibition of both interleukin-6 (IL-6)- and IL-1β-stimulated haptoglobin, serum amyloid A, and fibrinogen β gene expression in hepatocytes. Furthermore, induction of the hepatic inflammatory response was significantly exacerbated in HepG2 cells expressing short hairpin RNA targeting LRH-1 expression. Moreover, transient-transfection experiments and electrophoretic mobility shift and chromatin immunoprecipitation assays revealed that LRH-1 regulates this cytokine-elicited inflammatory response by, at least in part, antagonizing the CCAAT/enhancer binding protein β signaling pathway. Finally, we show, by using LRH-1 heterozygous mice, that LRH-1 is involved in the control of the inflammatory response at the hepatic level in vivo. Taken together, our results outline an unexpected role for LRH-1 in the modulation of the hepatic acute-phase response.
机译:据报道,孤儿核受体肝受体同源物1(LRH-1)在胆汁酸的生物合成和胆固醇逆向转运中起重要作用。在这里,我们显示LRH-1是控制肝急性期反应的关键因素。 LRH-1与腺病毒异位表达可强烈抑制肝细胞中白介素6(IL-6)和IL-1β刺激的触珠蛋白,血清淀粉样蛋白A和纤维蛋白原β基因的表达。此外,在表达靶向LRH-1表达的短发夹RNA的HepG2细胞中,肝炎性反应的诱导显着加剧。此外,瞬时转染实验以及电泳迁移率变化和染色质免疫沉淀试验表明,LRH-1通过至少部分拮抗CCAAT /增强子结合蛋白β信号传导途径来调节这种细胞因子引起的炎症反应。最后,我们显示通过使用LRH-1杂合小鼠,LRH-1参与了体内肝脏水平上炎症反应的控制。综上所述,我们的结果概述了LRH-1在调节肝急性期反应中的出乎意料的作用。

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