Somatostatin stimulates colonic MUC2 expression through SSTR5-Notch-Hes1 signaling pathway.

Colonic mucus barrier is regarded as the first defense line against bacteria and antigens from directly attaching to the epithelium, which would further lead to intestinal inflammation activation and pathological conditions. As MUC2 mucin is the predominant component of the mucus, understanding the regulatory mechanisms of MUC2 is important for mucus barrier protection. Somatostatin has been found to play a role in colon protection through various manners. However, whether involves in colonic mucus barrier regulation is still unclear. The aim of this study is to investigate the effects and potential mechanisms of duanyu1942 on colonic MUC2 expression and mucus secretion. In vivo study, exogenous somatostatin (octreotide) administration effectively stimulated mice colonic MUC2 expression and mucus secretion. In human goblet-like cell LS174T cells, duanyu1942 exposure also significantly stimulated MUC2 expression and mucus secretion. Further studies indicated that duanyu1942 receptor 5 was significantly activated by whereas specific siRNA transfection of LS174T cells significantly blocked increase in MUC2 expression and mucus secretion. In addition, duanyu1942R5 agonist L817,818 also upregulated MUC2 expression and mucus secretion in LS174T cells. Mechanistic studies further demonstrated that MUC2 upregulation was dependent on Notch-Hes1 pathway suppression by detecting notch intracellular domain (NICD) and Hes1 proteins. Taken together, our findings suggested that duanyu1942 could participate in colonic mucus barrier regulation through signaling pathway. These findings provide a deep insight into the role of duanyu1942 on colonic mucus regulation under physiological conditions.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}