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Na+/H+ exchanger isoform NHE3 and NHERF adaptor protein expression, localization and function in the small and large intestine of CD45RB high transfer colitis
Author(s) -
Yeruva Sunil,
Goldstein Julia,
Lünnemann Maria,
Chen Mingmin,
Singh Anurag kumar,
Riederer Brigitte,
Gereke Marcus,
Bruder Dunja,
Manns Michael peter,
Seidler Ursula
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.570.9
Subject(s) - downregulation and upregulation , small intestine , pdz domain , inflammation , sodium–hydrogen antiporter , villin , colitis , chemistry , microbiology and biotechnology , brush border , medicine , endocrinology , biology , sodium , biochemistry , membrane , gene , actin , vesicle , organic chemistry
Backround The molecular mechanisms for inflammatory diarrhea are multifactorial and incompletely understood. Aim We investigated the expression, localization and function of the major intestinal sodium absorptive transporter, the Na + /H + exchanger NHE3, as well as its regulatory PDZ‐adapter proteins NHERF1 and PDZK1, in the small and large intestine of mice after induction of a CD45RB high transfer colitis. Results After colitis induction, TNF‐alpha levels were increased both in the inflamed colon and microscopically normal‐appearing small intestine. NHE3 mRNA expression was upregulated in the colon and unaltered in the small intestine, NHE3 protein expression and localization in the brush border membrane (BBM) was not altered, but acid‐activated NHE3 transport rates in small intestinal villous and colonic surface cells were severely decreased, and fluid absorption in vivo was decreased in the small intestine. PDZK1 mRNA expression was downregulated, whereas that of NHERF1 was not altered. Glucocorticoid treatment of colitic mice for 4 days decreased colonic mucosal cytokine expression and increased PDZK1 expression as well as fluid absorption. Conclusion We suggest that during immune‐mediated intestinal inflammation, NHE3 BBM protein abundance is normal, but the regulation of its transport activity is disturbed. PDZK1 downregulation during inflammation may be one factor responsible for inflammation‐associated NHE3 dysfunction