title: Luminal regulation of Na(+)/H(+) exchanger gene expression in rat ileal mucosa.
abstract: 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.
authors.affiliation: Department of Surgery, Brigham and Women's Hospital, VA Boston Healthcare System, Boston, MA 02115, USA. dsoybel@partners.org
authors.forename: Marc A
authors.initials: MA
authors.lastname: Doble
authors.forename: Vicky B
authors.initials: VB
authors.lastname: Tola
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Chamberlain
authors.forename: Robert R
authors.initials: RR
authors.lastname: Cima
authors.forename: Alfred
authors.initials: A
authors.lastname: Van Hoek
authors.forename: David I
authors.initials: DI
authors.lastname: Soybel
mesh_terms: 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
chemical_list: C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers