Upregulation of CFTR expression but not SLC26A3 and SLC9A3 in ulcerative colitis.
In inflamed colonic mucosa, the equilibrium between absorptive and secretory functions for electrolyte and salt transport is disturbed. We compared the expression of three major mediators of the intestinal salt transport between healthy and inflamed colonic mucosa to understand the pathophysiology of diarrhea in inflammatory bowel disease. Expression levels of the cystic fibrosis transmembrane regulator (CFTR) (Cl- channel), SLC26A3 (Cl-/HCO exchanger) and SLC9A3 (Na+/H+ exchanger) mRNAs were measured by real-time quantitative RT-PCR in peroperative colonic samples from controls (n = 4) and patients with ulcerative colitis (n = 10). Several samples were obtained from each individual. Tissue samples were divided into three subgroups according to their histological degree of inflammation. Expression of CFTR and SLC26A3 proteins were determined by immunohistochemistry and Western blotting from the same samples, respectively. Increased expression of CFTR mRNA was observed in all three groups of affected tissue samples, most pronounced in mildly inflamed colonic mucosa (5-fold increase in expression; P < 0.001). The expression of the CFTR protein was detected from health and inflamed colon tissue. Although the expression of the SLC26A3 mRNA was significantly decreased in severe ulcerative colitis (P < 0.05), the SLC26A3 protein levels remained unchanged in all groups. The expression of SLC9A3 mRNA was significantly changed between the mild and severe groups. Intestinal inflammation modulates the expression of three major mediators of intestinal salt transport and may contribute to diarrhea in ulcerative colitis both by increasing transepithelial Cl- secretion and by inhibiting the epithelial NaCl absorption.
Department of Medical Genetics, Helsinki University Central Hospital, Biomedicum, University of Helsinki, 00014 Helsinki, Finland. hannes.lohi@helsinki.fi
H
H
Lohi
S
S
Mäkelä
K
K
Pulkkinen
P
P
Höglund
M-L
ML
Karjalainen-Lindsberg
P
P
Puolakkainen
J
J
Kere
D017920:Antiporters; D002352:Carrier Proteins / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters; D003093:Colitis, Ulcerative / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000378:metabolism / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism / Q000503:physiopathology; D008565:Membrane Proteins / Q000378:metabolism*; D012016:Reference Values; D012720:Severity of Illness Index; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D000076988:Sulfate Transporters; D015854:Up-Regulation
D017920:Antiporters; C505032:CFTR protein, human; D002352:Carrier Proteins; D027963:Chloride-Bicarbonate Antiporters; D008565:Membrane Proteins; C081011:SLC26A3 protein, human; C000613385:SLC9A3 protein, human; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D000076988:Sulfate Transporters; D019005:Cystic Fibrosis Transmembrane Conductance Regulator