Background and Aims : Recent evidence has implicated the involvement of aquaporins in cellular functions that are unrelated to transepithelial water transport. Although aquaporins are expressed in the gastrointestinal tract, their importance has so far been unclear. Aquaporin-3 (AQP3) is a water/glycerol transporter expressed at the basolateral membrane of colonic epithelial cells. The aim of this study was to investigate the involvement of AQP3 in enterocyte proliferation using a mouse model of inflammatory bowel disease.
Methods : Expression and function of AQP3 in colonic epithelium were established. Colitis was induced in wildtype and AQP3 null mice by oral dextran sulfate administration and intracolonic acetic acid administration. Outcome measures included clinical disease severity, survival, pathology and cellular responses. Some mice were administered glycerol to test whether disease progression could be altered.
Results : AQP3 null mice given dextran sulfate developed severe colitis after 3 days, with colonic hemorrhage, marked epithelial cell loss, and death. Wildtype mice, which had comparable initial colonic damage as assessed by cell apoptosis, developed remarkably less severe colitis, surviving to >8 days. Cell proliferation was greatly reduced in AQP3 null mice. Oral glycerol administration significantly improved survival and reduced the severity of colitis in AQP3 null mice. Mouse survival was also reduced in AQP3 null mice in the acetic acid model.
Conclusions : Our results implicate a novel role for AQP3 in enterocyte proliferation that is likely related to the glycerol transporting role of AQP3. AQP3 is thus a potential target for therapy of intestinal diseases associated with enterocyte destruction.
- cell proliferation
- transgenic mouse