肌成纤维细胞（MFB）的大量生成与活化是肝纤维化（HF）发生的核心环节，大量研究已证实肝细胞经上皮间质转化（EMT）可转变为MFB。我们前期研究发现姜黄素（Cur）能有效抑制肝细胞EMT进程，并能影响Hedgehog（Hh）信号通路与细胞自噬抑制HSC的活化。本项目创新性提出Cur抑制肝细胞EMT的作用与影响细胞的自噬水平相关，具体机制可能涉及到对Hh信号通路的调控。为此，本研究拟利用CCL4、BDL致HF与自噬基因干扰细胞模型，首先明确自噬与Cur抑制肝细胞EMT之间的关系；然后通过体内外激动或抑制Hh信号通路，研究Cur对肝细胞自噬与EMT的影响，以阐明Cur通过影响Hh信号通路调控自噬进而抑制肝细胞EMT的机制；最后利用自噬基因干扰小鼠进一步验证Cur调控自噬抑制肝细胞EMT的作用。本项目从新的视角阐释了Cur抗HF的作用机制，预期研究结果将为抗HF药物的临床治疗提供新的策略。

Myofibroblast (MFB) proliferation and activation is the key event in hepatic fibrosis (HF). A large number of studies have confirmed that hepatocytes can be transformed into MFB through epithelial-mesenchymal transformation (EMT). Our previous studies showed that Curcumin (Cur) can effectively inhibit hepatocyte EMT, as well as inhibit HSC activation and proliferation by affecting the Hedgehog (Hh) signaling pathway and autophagy. We herein innovatively put forward that Cur inhibition of the hepatocyte EMT is due to the regulation of cell autophagy. The involved mechanism may be affecting the Hh signal transduction pathways. To test this hypothesis, we will first use HF models induced by CCL4, BDL and MMH cell model interference autophagy genes, to investigate the relationship between autophagy and Cur inhibition of hepatocyte EMT; Then the effect of Cur regulating autophagy and EMT of hepatocyte will be examined under the condition of activation or inhibition of Hh signaling pathways in vivo and in vitro. The purpose of these studies are to clarify the mechanism of Cur regulation of cell autophagy and suppression of hepatocyte EMT by influencing the Hh signaling pathways. Finally we will use Cre; ATG7fl/fl mice to further verify the effect of Cur inhibition of hepatocyte EMT by regulating autophagy. Through those studies, we can interpret the mechanism of Cur reduction of HF from a new perspective, and the results of this study will provide new strategies for pharmacotherapy of hepatic fibrosis in clinical context.