LncRNA XR_378418竞争性结合miR-193a-3p调控PDGFR-α参与肝纤维化发病的机制及疏肝健脾方的干预作用

肝星状细胞（HSC）的激活和增殖是肝纤维化（HF）发生的中心环节，长链非编码RNA（LncRNA）参与调控HSC活化。前期研究表明，Lnc XR_378418是HF发病的关键LncRNA，可竞争性结合miR-193a-3p，调控PDGFR-α表达；疏肝健脾方能够下调Lnc XR_378418表达，防治HF。基于此，课题组提出“XR_378418通过竞争性结合miR-193a-3p，上调PDGFR-α表达，参与HF发病；疏肝健脾方通过调控XR_378418/miR-193a-3p/PDGFR-α信号轴，抑制HSC活化与增殖”的假说。本课题将以ceRNA理论为指导，XR_378418/miR-193a-3p/PDGFR-α信号轴为主线，HSC活化增殖为切入点，从“整体→器官→细胞”不同水平，阐释XR_378418参与HF的发病机制及疏肝健脾方的干预作用，为HF治疗提供潜在靶点及中药研究思路。

Activation and proliferation of hepatic stellate cells is the central event in hepatic fibrosis (HF), which long non-coding RNAs (lncRNAs) are likely key contributors to the activation. In our preliminary studies, XR_378418, a key LncRNA involved in development of HF, promotes the PDGFR-α expression with competitively binding miR - 193a-3p and inhibits activation of hepatic stellate cells; Shuganjianpi formula displayed good therapeutic effects on liver fibrosis and controls the expression of LncRNA, PDGFR-α and miR-193a-3p. Based on this work, we speculated that Lnc XR_378418 inhibits activation of hepatic stellate cells through promotion of the PDGFR-α expression with competitively binding miR-193a-3p; Shuganjianpi formula can treat HF and inhibit the proliferation and migration of hepatic stellate cells, by regulating the expression of Lnc XR_378418/PDGFR-α/miR-193a-3p. Therefore, in-depth study of the critical issues for the molecular mechanism of Lnc XR_378418 involved in hepatic fibrosis and Shuganjianpi formula treatment was carried out, which based on ceRNA theory and the signal axis of Lnc XR_378418/miR-193a-3p/PDGFR-α as the main line, the activation and proliferation of hepatic stellate cells as the entry point, from different levels of “body → organ → cell”. Implementation of the project should help to provide potential therapeutic targets and the Chinese medicine research ideas for HF treatment.