Abstract
Glucagon-like peptide 2 (GLP-2) is a potent intestine-specific growth factor. To determine whether GLP-2 has a direct effect on cellular proliferation, we examined the effects of GLP-2 on three different intestinal epithelial cell lines: Caco-2, T84, and IEC-6. Proliferation was assessed by measuring [3H]thymidine incorporation into cellular DNA. The expression of the cell cycle regulators cyclins D1, E, and A was determined by western blotting. GLP-2 stimulated [3H]thymidine incorporation in Caco-2 and T84 cells but not in IEC-6 cells. In Caco-2 cells, increased [3H]thymidine incorporation was detectable by day 1 and was maximal at day 5 following initiation of daily GLP-2 administration. Increased [3H]thymidine incorporation persisted for three days following treatment with a single dose of GLP-2. GLP-2 administration resulted in the induction of cyclins D1, E, and A in Caco-2 cells. These results suggest that GLP-2 acts directly on human intestinal epithelial cells to stimulate their proliferation.
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REFERENCES
Taylor RG, Fuller PJ: Humoral regulation of intestinal adaptation. Clin Endocrinol Metabol 8:165–184, 1994
Gordon JI: Understanding gastrointestinal epithelial cell biology: Lessons from mice with help from worms and flies. Gastroenterology 104:315–324, 1992
Hodin RA, Meng S, Nguyen D: Immediate-early gene expression in EGF-stimulated epithelial cells. J Surg Res 56:500–504, 1994
Filmus J, Shi W, Spencer T: Role of transforming growth factor alpha in the transformation of ras-transfected rat intestinal epithelial cells. Oncogene 8:1017–1022, 1993
Ko TC, Beauchamp RD, Townsend CM, Thompson EA, Thompson JC: Transforming growth factor-? inhibits rat intestinal cell growth by regulating cell cycle specific gene expression. Am J Surg 167:14–20, 1994
Dignass AU, Tsunekawa S, Podolsky DK: Fibroblast growth factors modulate intestinal epithelial cell growth and migration. Gastroenterology 106:1254–1262
Bristol JB, Williamson RCN: Mechanisms of intestinal adaptation. Pediatr Surg Int 4:233–241, 1988
Bloom SR: An enteroglucagon tumor in man. Gut 13:520–523, 1972
Gleeson MH, Bloom SR, Polak JM, Henry K, Dowling RH: Endocrine tumour in kidney affecting small bowel structure, motility an absorptive function. Gut 12:773–782, 1971
Drucker DJ, Ehrlich P, Asa SL, Brubaker PL: Induction of intestinal epithelial proliferation by glucagon like peptide 2. Proc Natl Acad Sci USA 93:7911–7916, 1996
Tsai C, Hill M, Asa SL, Brubaker PL, Drucker DJ: Intestinal growth-promoting properties of glucagon-like peptide-2 in mice. Am J Physiol 273:E77–E84, 1997
Litvak DA, Hellmich MR, Evers M, Banker NA, Townsend CM: Glucagon-like peptide-2 is a potent growth factor for small intestine and colon. J Gastrointest Surg 2:146–150, 1998
Drucker DJ, Yusta B, Boushey RP, DeForest L, Brubaker PL: Human [Gly2]GLP-2 reduces the severity of colonic injury in a murine model of experimental colitis. Am J Physiol 276:G79–G91, 1999
Boushey RP, Yusta B, Drucker DJ: Glucgon-like peptide 2 decreases mortality and reduces the sensitivity of Indomethacininduced murine enteritis. Am J Physiol 277:E937–E947, 1997
Bernard N, MacNaughton W, Scott R, Kirk D, Meddings JB: Glucagon-like peptide-2 (GLP-2) accelerates healing of indomethacin-induced enteritis. Gastroenterol 116:A122, 1999
Scott RB, Kirk D, MacNaughton WK, Meddings JB: GLP-2 augments the adaptive response to massive intestinal resection in rat. Am J Physiol 275:G911–G921, 1998
Holst JJ: Gut glucagon, enteroglucagon, gut glucagonlike immunoreactivity, glicentin-current status. Gastroenterology 84:1602–1613, 1983
Brubaker PJ, Lee YC, Drucker DJ: Alterations in proglucagon processing and inhibition of proglucagon gene expression. J Biol Chem 267:20728–20733, 1992
Fuller PJ, Beveridge DJ, Taylor RG: Ileal proglucagon gene expression in the rat: characterization in intestinal adaptation using in situ hybridization. Gastroenterol 104:459–466, 1993
Taylor RG, Verity K, Fuller PJ: Ileal glucagon gene expression: Ontogeny and response to massive small bowel resection. Gastroenterology 99:724–729, 1990
Yusta B, Huang L, Munroe D, Wolff G, Fantaske R, Sharma S, Demchyshyn L, Asa SL, Drucker DJ: Enteroendocrine localization of GLP-2 receptor expression in humans and rodents. Gastroenterology 119:744–755, 2000
Munroe DG, Gupta AK, Kooshesh F, Vyas TB, Fizkalla G, Wang H, Demchyshyn L, Yang Z, Kamboj RK, Chen H, McCallum K, Sumner-Smith M, Drucker DJ, Crivici A: Prototypic G protein-coupled receptor for the intestinotrophic factor glucagon-like peptide-2. Proc Natl Acad Sci USA 96:1569–1573, 1996
Watanabe N, Matsuyama T, Namba M, Miuagawa J, Itoh H, Komatsu R, Kono N, Tarui S: Trophic effect of glucagon-(1–21)-peptide on the isolated rat ileal mucosal cells. Biochem Biophys Res Commun 152:1038–1044, 1988
Lund PK, Hoyt E, Simmons JG, Ulshen MH: Regulation of intestinal glucagon gene expression during adaptive growth of small intestine. Digestion 54:371–373, 1993
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Jasleen, J., Ashley, S.W., Shimoda, N. et al. Glucagon-Like Peptide 2 Stimulates Intestinal Epithelial Proliferation In Vitro. Dig Dis Sci 47, 1135–1140 (2002). https://doi.org/10.1023/A:1015062712767
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DOI: https://doi.org/10.1023/A:1015062712767