炎症性肠病（IBD）是一类发病机制尚不明确且缺乏有效治疗药物的慢性肠道炎症性疾病。探究IBD病理机制具有重要的理论价值和科学意义。在炎症反应中，间充质细胞与肠上皮细胞的互作在损伤修复过程中发挥着重要作用。Wnt和Hippo-Yap信号通路在肠上皮细胞中的激活是促进损伤修复的关键因素。然而，肠上皮细胞如何感知炎症间充质微环境信号来调控上皮的Wnt和Hippo-Yap信号通路的分子机制仍尚未明确。在前期工作中，发现炎症信号可以诱导肠道间充质细胞表达Islr；间充质Islr通过参与调控肠上皮细胞的Wnt和Hippo-Yap信号通路来促进损伤修复过程。在本项目中，拟利用间充质细胞Islr基因条件敲除小鼠模型、肠道干细胞谱系追踪小鼠模型、结合人类结肠炎组织样本系统探究间充质的Islr在肠炎中调控肠上皮再生过程的功能及其作用机制，为炎症性肠病的诊断、治疗、药物设计提供新的靶点和科学依据。

Inflammatory bowel disease (IBD) is a type of chronic inflammation in gut. Its pathogenesis is still unclear, consequently resulting in lack of valid drugs for IBD. It is highly significant and important to elucidate the mechanism underlying IBD pathogenesis. The interaction between mesenchymal and epithelial cells is important for epithelial repair during colitis. It is well-known that the activation of Wnt and Hippo-Yap signaling pathways in epithelial cells is critical for this process. However, it is largely unknown how epithelial cells sense mesenchymal signals to regulate the two signaling pathways. In our preliminary results, we found that inflammatory signals induced Islr expression in mesenchymal cells and that stromal Islr is involved in the regulation of Wnt and Hippo-Yap signaling pathways. In this proposal, we will utilize mesenchymal cells-specific Islr conditional knockout (cKO) mouse model, intestinal stem cell lineage tracing mouse model, and human IBD samples to investigate the functions and its molecular mechanism of Islr in regulating epithelial regeneration during colitis. It would provide scientific evidences for novel IBD diagnosis, therapeutic strategy and drug designation.