肠纤维化是IBD慢性病程中重要病理改变，目前缺少有效干预措施。我们前期研究证实，机械微环境的改变可直接促进纤维化进展，但机制尚不清楚。Piezo1是机械门控离子通道，我们发现Piezo1在肠上皮细胞中表达，是肠上皮细胞机械微环境的重要“感受器”，Piezo1阻断剂干预后，肠纤维化程度减轻。因此，我们推测Piezo1在肠纤维化进展中起重要作用。我们前期研究发现力学刺激可以导致上皮细胞EMT，给与Piezo1阻断剂后，EMT则被显著抑制，而EMT在肠纤维化进展中作用关键。可见，“机械信号—Piezo1—EMT”这一力学生物学机制很可能举足轻重。本课题重点探讨“机械信号-Piezo1”是否是EMT的关键及其调控机制，我们将在不同机械信号的刺激下，干预Piezo1以及下游关键信号通路Integrin-FAK、RhoA/ROCK-MLCK-Actin，进一步阐明肠纤维化的机制，为其治疗提供新的靶点。

Intestinal fibrosis is an important pathological change in the chronic course of IBD. At present, there is a lack of effective interventions. Our previous studies have confirmed that changes in the mechanical microenvironment can directly promote fibrosis progress, but the mechanism is still unclear. Piezo1 is a mechanically gated ion channel. We found that Piezo1 wass expressed in intestinal epithelial cells and was an important "sensor" in the mechanical microenvironment of intestinal epithelial cells. After intervention with Piezo1 blocker, the degree of intestinal fibrosis was reduced. Therefore, we speculate that Piezo1 plays an important role in the progression of intestinal fibrosis. Previous studies have shown that mechanical stimulation can induce EMT in epithelial cells, which plays a key role in the progression of intestinal fibrosis. After Piezo1 blocker was given, EMT was significantly inhibited. Therefore, the mechano-biological mechanism of "mechanical signal - Piezo1 - EMT" is likely to play an important role. This topic focuses on whether "mechanical signal-Piezo1" is the key of EMT and its regulation mechanism. We will perform scientific experiments, under the condition of different mechanical signals, by intervention of Piezo1 and downstream key signaling pathways Integrin-FAK, RhoA/ROCK-MLCK-Actin to prove the function and mechanism of EMT. This study will provide a new therapeutic target for IBD intestinal fibrosis.