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Decreased expression of apical Na + channels and basolateral Na + , K + ‐ATPase in ulcerative colitis
Author(s) -
Greig ER,
BootHandford RP,
Mani V,
Sandle GI
Publication year - 2004
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1613
Subject(s) - epithelial sodium channel , western blot , ulcerative colitis , gene isoform , epithelial polarity , immunohistochemistry , microbiology and biotechnology , protein subunit , chemistry , medicine , blot , in situ hybridization , endocrinology , biology , messenger rna , sodium , epithelium , pathology , biochemistry , gene , disease , organic chemistry
Impaired absorption of sodium (Na + ) and water is a major factor in the pathogenesis of diarrhoea in ulcerative colitis (UC). Electrogenic Na + absorption, present mainly in human distal colon and rectum, is defective in UC, but the molecular basis for this is unclear. The effect of UC on the expression of apical Na + channels (ENaC) and basolateral Na + , K + ‐ATPase, the critical determinants of electrogenic Na + transport, was therefore investigated in this study. Sigmoid colonic and/or proximal rectal mucosal biopsies were obtained from patients with mild to moderate UC, and patients with functional abdominal pain (controls). ENaC subunit expression was studied by immunohistochemistry, western blot analysis, and in situ hybridization, and Na + , K + ‐ATPase isoform expression was studied by immunohistochemistry, western blotting, and northern blot analysis. UC was associated with substantial decreases in the expression of the ENaC β‐ and γ‐subunit proteins and mRNAs, whereas the decrease in ENaC α‐subunit protein detected by immunolocalization was less marked. The levels of expression of Na + , K + ‐ATPase α 1 ‐ and β 1 ‐isoform proteins were also lower in UC patients than in controls, although there were no differences in Na + , K + ‐ATPase α 1 ‐ and β 1 ‐isoform mRNA levels between the two groups. Taken together, these results show that UC results mainly in decreased expression of the apical ENaC β‐ and γ‐subunits, as well as the basolateral Na + , K + ‐ATPase α 1 ‐ and β 1 ‐isoforms. In conclusion, these changes provide a basis for the low/negligible levels of electrogenic Na + absorption seen in the distal colon and rectum of UC patients, which contribute to the pathogenesis of diarrhoea in this disease. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.