Repeated exposure to water immersion stress reduces the Muc2 gene level in the rat colon via two distinct mechanisms.

The mucin family plays a number of important roles in intestinal homeostasis. Among its members, the gel-forming Muc2, produced in goblet cells, is a major component of mucus and contributes to intestinal barrier integrity. Whereas psychological stress is known to impair intestinal barrier, the effects of chronic or repeated stress on mucin expression and goblet cell differentiation have not been well documented. The present study first examined the effects of different levels of exposure (3 days, 1 and 2 weeks) to water immersion stress on intestinal mucin gene expression in rats, and then explored the mechanisms underlying the stress-induced decrease in the colonic Muc2 level. Repeated water immersion stress for 1 and 2 weeks decreased colonic Muc2 gene levels to 40% of that of non-stressed animals, while exposure to stress for 3 days induced only a 25% decrease. The goblet cell numbers counts in the colons of the 1- and 2-week stress groups, but not the 3-day stress group, were decreased to 85% of that in non-stressed animals. Cdx2 expression, a transcriptional factor related to Muc2 synthesis in the goblet cells, was decreased in all stress groups, whereas Rath1 and Klf4 expressions, transcriptional factors related to goblet cell differentiation in Notch signaling were decreased in the 1-week stress group. Collectively, the repeated exposure to water immersion stress decreases Muc2 synthesis in the goblet cells via decreased Cdx2 expression and subsequently reduces the goblet cell number via Notch signaling suppression.