Aquaporin expression is downregulated in a murine model of colitis and in patients with ulcerative colitis, Crohn’s disease and infectious colitis

Abstract

Colitis is associated with alterations in electrolyte and water transport. These changes give rise to some of the symptoms experienced by patients with colitis. Alterations in fluid flux may also contribute to increased susceptibility to mucosal injury. Recently, endogenous water channel proteins (aquaporins; AQPs), have been identified in colonic tissue. The expression of AQP4, AQP7 and AQP8 was examined, via reverse transcription/polymerase chain reaction, Western blotting and immunohistochemistry, in a murine model of colitis and in patients with inflammatory bowel disease or infectious colitis. Colitis was induced in C57BL/6 mice by the addition of 2.5% dextran sodium sulphate (DSS) to their drinking water. AQP expression in these mice was assessed following 12 h to 7 days of DSS exposure and during the recovery phase from 1 to 15 days following cessation of DSS exposure. Colonic water transport was measured after 1 and 3 days of DSS and following 7 days of recovery. The expression of AQP4 and AQP8 mRNA was significantly decreased after 12-24 h of DSS exposure and remained depressed throughout the treatment period. Expression of AQP7 was more variable. Protein expression followed a similar pattern to that observed for AQP mRNA. Significant alteration in colonic fluid secretion was correlated with reduced expression of AQP isoforms. Significantly, patients with active ulcerative colonic, Crohn's colitis or infectious colitis had similar dramatic reductions in AQP expression that appeared to be correlated with disease activity. Thus, colonic injury in both mouse and man is associated with a downregulation in AQP expression.

Shp2/MAPK signaling controls goblet/paneth cell fate decisions in the intestine

“…S1H). These genes are known to be down-regulated in human and mouse colitis (24). The data thus show that the Shp2 mutation in the intestine results in goblet cell deficits and colitis.…”

Immunohistochemical localization of aquaporin 4 (AQP4) in the porcine gastrointestinal tract

“…In humans, lower expression of AQP4 in colonic mucosa is correlated with the development of slow transit constipations (Wang et al 2010). Changes in expression levels of AQP4 were additionally observed in inflammatory diseases such as colitis (Hansen et al 2009), ulcerative colitis and Crohn's disease (Hardin et al 2004).…”

Critical Role of Aquaporins in Interleukin 1β (IL-1β)-induced Inflammation

“…We observed that AQP1 deficiency reduces neutrophilic inflammation as well as cytokine release in silica-induced lung inflammation. Besides the respiratory tract, AQPs have been associated with inflammation in other organs (38,39). In a model of peritoneal dialysis, reduced accumulation of leukocytes was observed in mice genetically deficient in AQP1 (40).…”