Transfection of the sodium/glucose cotransporter into colon mucosa: a novel treatment for short bowel syndrome.
OBJECTIVE
Short bowel syndrome results from small intestine loss but frequently is associated with survival of the colon. This study was designed to determine if colonic mucosa could be induced to absorb galactose by tranfection of the sodium glucose cotransporter, SGLT-1 into a colonic segment.


METHODS
Using 10 rats, a 7-cm segment of colon was infused for 1 hour with a solution containing 50 microg/mL of a plasmid with or without an SGLT-1 insert. An 80% small bowel resection was performed, and the segment was interposed into the small bowel. On the third day [14C] galactose absorption was measured. Mucosal RNA was extracted, and relative band intensities were measured using primers for SGLT-1. Statistical analysis was performed using the Student's t test and expressed as mean +/- SEM.


RESULTS
Rats transfected with the SGLT-1 plasmid showed a significant increase (194%) in galactose absorption compared with controls. Transfected animals also showed high levels of of SGLT-1 transcription when compared with controls (792% increase).


CONCLUSIONS
These data show that in vivo exposure of colon mucosa to a plasmid containing SGLT-1 allows transfer of that gene into enterocytes. Expression of SGLT-1 can create an absorptive segment that may in part alleviate the malabsorption associated with short bowel syndrome.
Pearson
Philip Y
PY
Department of Surgery, A.I. duPont Hospital for Children, Wilmington, DE 19803, USA.
Yu
Dahong
D
Schwartz
Marshall Z
MZ
D000818:Animals; D003106:Colon / Q000378:metabolism*; D005690:Galactose / Q000493:pharmacokinetics*; D015316:Genetic Therapy; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012778:Short Bowel Syndrome / Q000378:metabolism* / Q000628:therapy*; D051269:Sodium-Glucose Transporter 1; D014162:Transfection
D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D005690:Galactose