| First Author | Moeser AJ | Year | 2008 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 295 |
| Issue | 4 | Pages | G791-7 |
| PubMed ID | 18719001 | Mgi Jnum | J:142279 |
| Mgi Id | MGI:3820804 | Doi | 10.1152/ajpgi.00538.2007 |
| Citation | Moeser AJ, et al. (2008) Mice lacking the Na+/H+ exchanger 2 have impaired recovery of intestinal barrier function. Am J Physiol Gastrointest Liver Physiol 295(4):G791-7 |
| abstractText | Ischemic injury induces breakdown of the intestinal barrier. Recent studies in porcine postischemic tissues indicate that inhibition of NHE2 results in enhanced recovery of barrier function in vitro via a process involving interepithelial tight junctions. To further study this process, recovery of barrier function was assessed in wild-type (NHE2(+/+)) and NHE2(-/-) mice in vivo and wild-type mice in vitro. Mice were subjected to complete mesenteric ischemia in vivo, after which barrier function was measured by blood-to-lumen mannitol clearance over a 3-h recovery period or measurement of transepithelial electrical resistance (TER) in Ussing chambers immediately following ischemia. Tissues were assessed for expression of select junctional proteins. Compared with NHE2(+/+) mice, NHE2(-/-) mice had greater intestinal permeability during the postischemic recovery process. In contrast to prior porcine studies, pharmacological inhibition of NHE2 in postischemic tissues from wild-type mice also resulted in significant reductions in TER. Mucosa from NHE2(-/-) mice displayed a shift of occludin and claudin-1 expression to the Triton-X-soluble membrane fractions and showed disruption of occludin and claudin-1 localization patterns following injury. This was qualitatively and quantitatively recovered in NHE2(+/+) mice compared with NHE2(-/-) mice by the end of the 3-h recovery period. Serine phosphorylation of occludin and claudin-1 was downregulated in NHE2(-/-) postischemia compared with wild-type mice. These data indicate an important role for NHE2 in recovery of barrier function in mice via a mechanism involving tight junctions. |
