Mice lacking the Na+/H+ exchanger 2 have impaired recovery of intestinal barrier function

Adam J. Moeser, Prashant K. Nighot, Kathleen A. Ryan, Janet E. Simpson, Lane L. Clarke, Anthony T. Blikslager

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

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 post-ischemic 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.

Original languageEnglish (US)
Pages (from-to)G791-G797
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume295
Issue number4
DOIs
StatePublished - Oct 2008

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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