Differential expression of endothelin-2 along the mouse intestinal tract

Endothelin (ET)-2, an ET family peptide, is highly expressed in intestine. However, the specific distribution and function of ET-2 remain unknown. We elucidated the expression profile and localization of ET-2 in mouse gastrointestinal tract. Real-time PCR analysis revealed that ET-2 gene expression in the gastrointestinal tract of healthy animals was relatively high in the colon. Immunohistochemical analysis revealed ET-2-like immunoreactivity mainly in epithelial cells of the mucosa throughout the intestinal tract of healthy animals. Intracellularly, ET-2 was concentrated close to the basement membrane of intestinal epithelial cells. A weak ET-2-like immunoreactivity was also localized to some neurofibers and the myenteric plexus of the muscle layer, coexpressing with vasoactive intestinal peptide. ET-2-like immunoreactivity was also detected at Brunner's glands of the duodenum and follicle-associated epithelium of Peyer's patch. In contrast, ET-1-like immunoreactivity was uniformly distributed in epithelial cells. In dextran sulfate sodium (DSS)-induced colitis, colonic ET-2 was upregulated during the late stage of DSS treatment. These results suggest that in intestinal epithelial cells ET-2 could be secreted into the lamina propria and the dome region in Peyer's patch, and that it might modulate immune cells in these sites for mucosal defense.