The mucus layer coating the gastrointestinal tract serves as the first line of intestinal defense against
infection and injury. Probiotics promote
mucin production by goblet cells in the intestine. p40, a Lactobacillus rhamnosus GG-derived soluble
protein, has been shown to transactivate the
EGF receptor (EGFR) in intestinal epithelial cells, which is required for inhibition of apoptosis and preservation of barrier function in the colon, thereby ameliorating intestinal injury and
colitis. Because activation of EGFR has been shown to up-regulate
mucin production in goblet cells, the purpose of this study was to investigate the effects and mechanisms of p40 regulation of
mucin production. p40 activated EGFR and its downstream target, Akt, in a concentration-dependent manner in LS174T cells. p40 stimulated Muc2 gene expression and
mucin production in LS174T cells, which were abolished by inhibition of EGFR
kinase activity, down-regulation of EGFR expression by EGFR
siRNA transfection, or suppression of Akt activation. Treatment with p40 increased
mucin production in the colonic epithelium, thus thickening the mucus layer in the colon of wild type, but not of Egfr(wa5) mice, which have a dominant negative mutation in the EGFR
kinase domain. Furthermore, inhibition of
mucin-type O-linked glycosylation suppressed the effect of p40 on increasing
mucin production and protecting intestinal epithelial cells from TNF-induced apoptosis in colon organ culture. Thus, these results suggest that p40-stimulated activation of EGFR mediates up-regulation of
mucin production, which may contribute to the mechanisms by which p40 protects the intestinal epithelium from injury.