Molecular mechanisms by which casein glycomacropeptide maintains internal homeostasis in mice with experimental ulcerative colitis.

• Main Authors: Yongbo Cui, Chenchen Zhu, Zhu Ming, Jiangming Cao, Yali Yan, Pei Zhao, Guangchang Pang, Zixin Deng, Yi Yao, Qingsen Chen
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2017-01-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC5507290?pdf=render

OBJECTIVES:The aim of this study was to elucidate the molecular mechanisms by which food-derived casein glycomacropeptide (CGMP) maintains internal homeostasis in the intestinal mucosa and to investigate the effects of CGMP on the intestinal mucosal immunological barrier and related signal transduction pathways. METHODS:In this study, a famoxadone (OXZ)-induced mouse experimental ulcerative colitis (UC) model was built. The experimental UC mice were intragastrically administered milk-derived CGMP for four consecutive days. The molecular mechanisms by which milk-derived CGMP improved and restored the inflammatory status in UC symptoms were elucidated by H&E staining, immunohistochemical staining and western blotting. RESULTS:The results indicated that CGMP (50 mg/(kg bw·d)) could significantly improve morphological injury to intestinal mucosa in OXZ-induced UC mice to the same extent that did sulfasalazine (SASP, 40 mg/(kg bw·d)), a medicine used to treat UC, in the control group. The study found that CGMP could significantly reduce the expression of Human mucosal addressin cell adhesion molecule-1 (MAdCAM-1), Cluster of differentiation 4 (CD4) and Cluster of differentiation 8 (CD8) in the lamina propria of the intestinal mucosa and significantly stimulate the secretion of sIgA to increase intestinal immunity. Furthermore, CGMP was found to be directly involved in inhibiting the MAPK pathway and activating the TGF-β1/Smad signal transduction cascade, which could maintain immunological regulation of the intestinal mucosa and protect the functions of the intestinal mucosal barrier. CONCLUSIONS:This study elucidated the molecular mechanisms by which CGMP maintained homeostasis of the intestinal mucosa and further confirmed its pharmaceutical value as a food-derived functional component with promising potential for further exploration/utilization.