潘氏细胞是肠干细胞微环境的主要细胞成分，是干细胞命运的决定因素，机体调节潘氏细胞的功能靶点复杂不清。我们发现：小鼠小肠潘氏细胞表达雌激素膜受体GPER，GPER激活促进潘氏细胞成熟及离体肠上皮再生；抑制潘氏细胞Wnt3分泌，显著抑制GPER激活诱导的干细胞增殖基因表达上调；GPER激活上调潘氏细胞Wnt3、Wnt信号靶基因MMP-7表达；在体实验发现GPER激活减轻化疗性肠损伤模型的体重下降和小肠粘膜损伤，增加潘氏细胞数目及ß-catenin表达。我们推测：雌激素结合潘氏细胞GPER，通过调节Wnt信号途径诱导潘氏细胞成熟，调节肠干细胞微环境，参与生理肠上皮再生和病理肠粘膜修复。拟利用Lgr5-EGFP-IRES-CreERT2小鼠、潘氏细胞缺陷小鼠，从组织、细胞、分子水平在生理/病理条件下对假设进行研究。揭示一个全新的潘氏细胞功能调节靶点，为肠上皮再生及损伤治疗提供新思路。

As the key component of intestinal stem cell niche, paneth cell determines the fate of intestinal stem cell. However, the target that regulates the function of paneth cell is unclear. Our preliminary experiments showed firstly: ① There was expression of GPER on paneth cell at C57BL/6 mice. Activation of GPER prompted the maturation of paneth cell in vivo and epithelial regeneration in organic culture. ② GPER activation up-regulated the expression of Wnt target gene c-myc. Inhibition of Wnt3 secretion from paneth cell blocked the up-regulation of c-myc expression induced by GPER activation in organic culture. ③ GPER activation enhanced the production of Wnt3 mRNA and MMP-7 mRNA in paneth cell. ④ GPER activation alleviated weight loss and intestinal mucositis induced by 5-Fu in vivo. Furthermore, the number of paneth cell, ß-catenin protein expression and intestinal stem cell marker gene were also up-regulated by GPER activation in intestinal injury model. Thus, we suppose that estrogen combines with GPER to induce the maturation of paneth cell via up-regulating the Wnt effectors. GPER is involved in the maintenance of intestinal epithelial regeneration in physiological and pathophysiological situation via niche dependent pathway. Thus, we design to prove the hypothesis and explore the molecular mechanism with Lgr5-EGFP-IRES-CreERT2 mice and paneth cell deficiency mice at the level of whole body, tissue and cell in physiological/pathophysiological state. The research results will reveal a novel mechanism that maintains the paneth cell function and provide a new target for treatment of disease induced by intestinal stem cell injury.