MicroRNA介导HMGB1-HNF1A环路参与肝细胞与肝星状细胞互调控的分子机制研究

Restoration of hepatocytes function through attenuating liver injury has been recognized as an effective step for the hepatic fibrosis reversal in a certain context. The mutual regulation between hepatocytes damage and the activation and proliferation of hepatic stellate cell (HSC) is the internal regulatory factor of hepatic fibrosis deterioration. Intensive study of the underlying mechanism has become one of research hotspots to explore effective treatment strategies for hepatic fibrosis. The mutual regulation between the high mobility group protein B1 (HMGB1) and hepatocyte nuclear factor 1A (HNF1A) as the starting point, combined with high-throughput sequencing of microRNA, we search for the molecular mechanism of mutual regulation between hepatocytes damage and the activation and proliferation of HSC through rat liver fibrosis model, co-culture of normal hepatocytes and HSCs, and interactions of protein with DNA, microRNA with mRNA on multiple aspects of animal, cell and molecule. This research reveals miR-146b/miR-19b mediated HMGB1-HNF1A loop involved in the mutual regulation of liver injury and activation and proliferation of HSC, and provides a theoretical basis for screening the indexes of liver injury and hepatic fibrosis diagnosis and discovery of new therapeutic targets.

控制肝细胞损伤被公认为是肝纤维化在一定程度上逆转的有效措施，肝细胞损伤与肝星状细胞活化增殖之间的互调控是肝纤维化恶化的内在调控因素。深入研究这两者之间的调控机制成为目前探索肝纤维化转归的有效治疗策略中的研究热点之一。本课题以高迁移率族蛋白B1（HMGB1）与肝细胞核因子 1A（HNF1A）之间的互调控为出发点，结合microRNA高通量测序，从大鼠肝纤维化模型，正常肝细胞与肝星状细胞共培养，以及蛋白与DNA，microRNA与mRNA相互作用等动物、细胞与分子多个层面寻找调控肝细胞与肝星状细胞互调控的分子机制。本课题揭示miR-146b/miR-19b介导HMGB1-HNF1A的环路可参与肝细胞损伤与HSC活化增殖之间的互调控，为筛选肝细胞损伤和肝纤维化诊断的指标及小分子治疗靶点提供理论依据。

控制肝细胞损伤被公认为是肝纤维化在一定程度上逆转的有效措施，肝细胞损伤与肝星状细胞活化增殖之间的互调控是肝纤维化恶化的内在调控因素。深入研究这两者之间的调控机制成为目前探索肝纤维化转归的有效治疗策略中的研究热点之一。本课题以高迁移率族蛋白B1（HMGB1）与肝细胞核因子 1A（HNF1A）之间的互调控为出发点，结合microRNA高通量测序，从大鼠肝纤维化模型，正常肝细胞与肝星状细胞共培养，以及蛋白与DNA，microRNA与mRNA相互作用等动物、细胞与分子多个层面寻找调控肝细胞与肝星状细胞互调控的分子机制。本课题揭示miR-146b介导HMGB1-HNF1A的环路可参与肝细胞损伤与HSC活化增殖之间的互调控，为筛选肝细胞损伤和肝纤维化诊断的指标及小分子治疗靶点提供理论依据。