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Am J Physiol Gastrointest Liver Physiol (August 14, 2003). doi:10.1152/ajpgi.00374.2002
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Submitted on August 30, 2002
Accepted on August 2, 2003

THE EFFECT OF GLP-2 ON MUCOSAL MORPHOLOGY AND SGLT1 EXPRESSION IN TISSUE-ENGINEERED NEOINTESTINE

Anthony Ramsanahie1, Mark Duxbury1, Tracy Grikscheit2, Alexander Perez1, David B. Rhoads3, James Gardner-Thorpe1, Jennifer Ogilvie2, Stanley W. Ashley1, Joseph P. Vacanti2, and Edward E. Whang1*

1 Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA
2 Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
3 Division of Endocrinology, Massachusetts General Hospital, Boston, Massachusetts, USA

* To whom correspondence should be addressed. E-mail: ewhang1{at}partners.org.

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). METHODS: 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 [Gly2]GLP-2 (twice daily, 1µg/g body weight), or vehicle alone (control) for 10 days. Rats were then killed and tissues harvested for analysis. SGLT1 mRNA expression was assessed with Northern blotting and in situ hybridization. SGLT1 protein was localized using immunofluorescence. RESULTS: GLP-2 administration resulted in 1.8-fold 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<0.05) 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. CONCLUSIONS: The response of tissue-engineered neointestine to exogenous GLP-2 includes mucosal growth and enhanced SGLT1 epxression. Tissue engineering principles may help in dissecting the regulatory mechanisms mediating complex processes in the intestinal epithelium.




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