Effect of GLP-2 on mucosal morphology and SGLT1 expression in tissue-engineered neointestine.
Using tissue-engineering techniques, we have developed a neointestine that regenerates the structural and dynamic features of native small intestine. In this study, we tested neointestinal responsiveness to glucagon-like peptide 2 (GLP-2). Neointestinal cysts were engineered by seeding biodegradable polymers with neonatal rat intestinal organoid units. The cysts were matured and anastomosed to the native jejunum of syngeneic adult recipients. Animals were treated with GLP-2 [Gly2] (twice daily, 1 microg/g body wt) or vehicle alone (control) for 10 days. Rats were then killed, and tissues were harvested for analysis. Na+-glucose cotransporter (SGLT1) mRNA expression was assessed with Northern blotting and in situ hybridization. SGLT1 protein was localized by using immunofluorescence. GLP-2 administration resulted in 1.8- and 1.7-fold increases (P < 0.05) in neointestinal villus height and crypt depth, respectively. GLP-2 administration also resulted in a 2.4-fold increase (P < 0.01) in neomucosal SGLT1 mRNA expression. SGLT1 mRNA expression was localized to enterocytes throughout the villi, and SGLT1 protein was localized to the brush border of enterocytes along the entire length of villi from the neointestine of GLP-2-treated animals. The response of tissue-engineered neointestine to exogenous GLP-2 includes mucosal growth and enhanced SGLT1 expression. Therefore, tissue-engineering principles may help in dissecting the regulatory mechanisms mediating complex processes in the intestinal epithelium.
Ramsanahie
Anthony
A
Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Duxbury
Mark S
MS
Grikscheit
Tracy C
TC
Perez
Alexander
A
Rhoads
David B
DB
Gardner-Thorpe
James
J
Ogilvie
Jennifer
J
Ashley
Stanley W
SW
Vacanti
Joseph P
JP
Whang
Edward E
EE
D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D051273:Glucose Transporter Type 2; D006801:Humans; D007413:Intestinal Mucosa / Q000033:anatomy & histology* / Q000187:drug effects* / Q000502:physiology; D007421:Intestine, Small / Q000033:anatomy & histology* / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D018027:Receptors, Glucagon / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1; D013393:Sucrase / Q000235:genetics; D023822:Tissue Engineering
C000593833:GLP1R protein, human; C000593835:Glp1r protein, rat; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D051273:Glucose Transporter Type 2; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; D010455:Peptides; D012333:RNA, Messenger; D018027:Receptors, Glucagon; C495674:SLC5A1 protein, human; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D004763:Glucagon-Like Peptides; D013393:Sucrase