WR-GLP2, a glucagon-like peptide 2 from hybrid crucian carp that protects intestinal mucosal barrier and inhibits bacterial infection.

Abstract

Glucagon-like peptide 2 (GLP2) is a proglucagon-derived peptide produced by intestinal enteroendocrine L-cells. The main biological actions of GLP2 in mammals are related to regulating energy absorption and maintaining the morphology, integrity of intestinal mucosa. However, the in vivo function of fish GLP2 in intestinal barrier and immune defense is essentially unknown. With an aim to elucidate the antimicrobial mechanism of GLP2 in fish, we in this study examined the function of GLP2 from hybrid crucian carp. Hybrid crucian carp GLP2 (WR-GLP2) possesses the conserved glucagon like hormones 2 domain. WR-GLP2 is mainly expressed in the intestine and is significantly upregulated after Aeromonas hydrophila infection. AB-PAS staining analysis showed WR-GLP2 significantly increased the number of goblet cells in intestine. WR-GLP2 induced significant inductions in the expression of the antimicrobial molecules (MUC2, Lyzl-1, Hepcidin-1 and LEAP-2) and tight junctions (ZO-1, Occludin and Claudin-4). In addition, WR-GLP2 significantly alleviated the intestinal apoptosis, thereby enhancing host's resistance against Aeromonas hydrophila infection. Together these results indicate that WR-GLP2 is involved in intestinal mucosal barrier and immune defense against pathogen infection.