Luminal regulation of Na(+)/H(+) exchanger gene expression in rat ileal mucosa.
It is well recognized that ileostomy patients suffer from chronic depletion of Na(+) through the stoma effluent. In this study we evaluated the effects of ileostomy on messenger RNA levels that encode different Na(+)/H(+) exchanger isoforms (NHE-2 and NHE-3). Loop ileostomies were created in Sprague-Dawley rats. Segments of diverted ileum were harvested for quantitation of mRNA levels encoding these isoforms and the Na(+)/K(+) ATPase in mucosal scrapings and for immunofluorescence microscopy, specifically of the NHE-3 protein. Our studies indicate that as early as 8 days after diversion, NHE-3 gene expression is selectively attenuated in poststomal ileal mucosa. Mucosal morphology remains undisturbed, and the distribution of protein expression along the crypt/villus axis is not altered. Infusion of Na(+) or the enterocyte nutrient, glutamine, into the lumen of the diverted segment restores or even augments mRNA levels for NHE-3, again without altering the histologic appearance or distribution of the protein along the crypt/villus axis. These effects are specific because nonpolar osmolytes (mannitol) and related organic nutrients not specific for the enterocyte (i.e., butyrate) have no effect on mRNA levels of NHE-3. Further work is required to understand how the early changes in mRNA contribute to mucosal function and response to luminal diversion.
Doble
Marc A
MA
Department of Surgery, Brigham and Women's Hospital, VA Boston Healthcare System, Boston, MA 02115, USA. dsoybel@partners.org
Tola
Vicky B
VB
Chamberlain
Stephanie A
SA
Cima
Robert R
RR
Van Hoek
Alfred
A
Soybel
David I
DI
D000818:Animals; D005786:Gene Expression Regulation / Q000502:physiology*; D007081:Ileostomy; D007082:Ileum / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D017136:Ion Transport; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D014158:Transcription, Genetic
C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers