期刊
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
卷 286, 期 2, 页码 G244-G252出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00141.2003
关键词
epithelial barrier; epithelial sodium channel; sodium chloride absorption; sodium/hydrogen exchanger 3; tight junction
Colitis in interleukin-2-deficient (IL-2(-/-)) mice resembles ulcerative colitis in humans. We studied epithelial transport and barrier function in IL-2(-/-) mice and used this model to characterize mechanisms of diarrhea during intestinal inflammation. Na-22(+) and Cl-36(-) fluxes were measured in proximal colon. Net Na+ flux was reduced from 4.0 +/- 0.5 to 0.8 +/- 0.5 mumol . h(-1) . cm(-2), which was paralleled by diminished mRNA and protein expression of the Na+/H+ exchanger NHE3. Net Cl- flux was also decreased from 2.2 +/- 1.6 to -2.7 +/- 0.6 mumol . h(-1) . cm(-2), indicating impaired Na+-Cl- absorption. In distal colon, aldosterone-induced electrogenic Na+ absorption was 6.1 +/- 0.9 mumol . h(-1) . cm(-2) in controls and was abolished in IL-2(-/-) mice. Concomitantly, mRNA expression of beta- and gamma-subunits of the epithelial sodium channel ( ENaC) was reduced. Epithelial barrier was studied in proximal colon by impedance technique and mannitol fluxes. In contrast to ulcerative colitis, epithelial resistance was increased and mannitol fluxes were decreased in IL-2(-/-) mice. This was in accord with the findings of reduced ion transport as well as increased expression of tight junction proteins occludin and claudin-1, -2, -3, and -5. In conclusion, the IL-2(-/-) mucosa exhibits impaired electroneutral Na+- Cl- absorption and electrogenic Na+ transport due to reduced mRNA and protein expression of NHE3 and ENaC beta- and gamma-subunit mRNA. This represents a model of early intestinal inflammation with absorptive dysfunction due to impaired transport protein expression/function while epithelial barrier is still intact. Therefore, this model is ideal to study regulation of transporter expression independent of barrier defects.
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