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Am J Physiol Gastrointest Liver Physiol (April 10, 2002). doi:10.1152/ajpgi.00356.2001
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Articles in PresS, published online ahead of print April 10, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00356.2001
Submitted on August 9, 2001
Accepted on April 3, 2002

Upregulation of CFTR expression but not SLC26A3 and SLC9A3 in ulcerative colitis

Hannes Lohi1*, Siru Makela1, Kati Pulkkinen1, Pia Hoglund2, Marja-Liisa Karjalainen-Lindsberg3, Pauli Puolakkainen4, and Juha Kere5

1 Department of Medical Genetics, University of Helsinki, Helsinki, Finland
2 Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland; Department of Medical Genetics, University of Helsinki, Helsinki, Finland
3 Department of Pathology, University of Helsinki, Helsinki, Finland
4 Department of Surgery, University of Helsinki, Helsinki, Finland
5 Finnish Genome Center, University of Helsinki, Helsinki, Finland; Department of Medical Genetics, University of Helsinki, Helsinki, Finland

* To whom correspondence should be addressed. E-mail: hannes.lohi{at}helsinki.fi.

Background- 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 diarrhoea in inflammatory bowel disease. Methods- Expression levels of the CFTR (Cl- -channel), SLC26A3 (Cl-/HCO3 - 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 the CFTR and SLC26A3 proteins were determined by immunohistochemistry and western blotting from the same samples, respectively. Results- 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 UC (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. Conclusions- Intestinal inflammation modulates the expression of three major mediators of intestinal salt transport and may contribute to diarrhoea in ulcerative colitis both by increasing transepithelial Cl- secretion and by inhibiting the epithelial NaCl absorption.




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