Effect of glucagon-like peptides-2 on LGR5 expression of intestinal mucosal stem cell and its protective role on intestinal mucosa in mice

Objective To explore the role of LGR5 positive intestinal stem cells in repairing damage of intestinal mucosa resulting from endotoxemia and to determine whether the damaged intestinal mucosa can be repaired by regulating the proliferation and differentiation of intestinal stem cells. Methods Wistar rats were randomly divided into control group, lipopolysaccharide (LPS) group, and glucagon-like peptides 2 (GLP-2) group. LPS was injected interaperitoneally into rats of the LPS group and GLP-2 group at a dose of 5 mg/kg (1 ml/kg); saline (1 ml/kg) was injected into the rats of control group. GLP-2 250 μg/kg (1 ml/kg) was injected into the rats of GLP-2 group 1 hour after the LPS injection. The terminal ilea were collected from 8 rats in each group at 6 h, 24 h, and 72 h post-LPS injection. Structural changes in the intestinal epthelium of every group were observed under the light microscope and electron microscope. The expression of LGR5 in intestinal stem cell was detected by immunohistochemical method and RT-PCR. Results In general, intestinal edema and hyperemia was observed in both LPS and GLP-2 groups at 6 h. Fracture and lodging of villi, infiltration of inflammatory cells, and visible exudate within the cavity were observed under light microscopy. The inflammatory injury was less severe in the GLP-2 group than in the LPS group at 6 h. The injury of intestina mucosa gradually repaired between 24 h and 72 h after injection of LPS in both LPS group and GLP-2 group. Importantly, samples taken from GLP-2 group and LPS group at the same time point indicated that the GLP-2 group recovered significantly better than the LPS group. And expressions of LGR5 mRNA in GLP-2 group at 6 h, 24 h, 72 h (0.13±0.05, 0.16±0.05, 0.16±0.04) were significantly higher than those in LPS group respectively (0.52±0.09, 0.73±0.14, 0.48±0.24), as shown by RT-PCR, and than that in control group (0.12±0.03) (P< 0.05). Conclusion Exogenous GLP-2 may facilitate intestinal stem cell proliferation, thereby promoting the recovery of intestinal mucosa damaged by endotoxemia. GLP-2 appears to promote stem cell proliferation, differentiation, and gradual migration of stem cells from the intestinal crypts to the damaged mucosa. Key words: Endotoxemia; Intestinal mucosa; Stem cells; Rat