Effect of Glucagon-like Peptide 2 on Tight Junction in Jejunal Epithelium of Weaned Pigs though MAPK Signaling Pathway
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The glucagon-like peptide 2 (GLP-2) that is expressed in intestine epithelial cells of mammals, is important for intestinal barrier function and regulation of tight junction (TJ) proteins. However, there is little known about the intracellular mechanisms of GLP-2 in the regulation of TJ proteins in piglets’ intestinal epithelial cells. The purpose of this study is to test the hypothesis that GLP-2 regulates the expressions of TJ proteins in the mitogen-activated protein kinase (MAPK) signaling pathway in piglets’ intestinal epithelial cells. The jejunal tissues were cultured in a Dulbecco’s modified Eagle’s medium/high glucose medium containing supplemental 0 to 100 nmol/L GLP-2. At 72 h after the treatment with the appropriate concentrations of GLP-2, the mRNA and protein expressions of zonula occludens-1 (ZO-1), occludin and claudin-1 were increased (p<0.05). U0126, an MAPK kinase inhibitor, prevented the mRNA and protein expressions of ZO-1, occludin, claudin-1 increase induced by GLP-2 (p<0.05). In conclusion, these results indicated that GLP-2 could improve the expression of TJ proteins in weaned pigs’ jejunal epithelium, and the underlying mechanism may due to the MAPK signaling pathway.
Abstract
The glucagon-like peptide 2 (GLP-2) that is expressed in intestine epithelial cells of mammals, is important for intestinal barrier function and regulation of tight junction (TJ) proteins. However, there is little known about the intracellular mechanisms of GLP-2 in the regulation of TJ proteins in piglets’ intestinal epithelial cells. The purpose of this study is to test the hypothesis that GLP-2 regulates the expressions of TJ proteins in the mitogen-activated protein kinase (MAPK) signaling pathway in piglets’ intestinal epithelial cells. The jejunal tissues were cultured in a Dulbecco’s modified Eagle’s medium/high glucose medium containing supplemental 0 to 100 nmol/L GLP-2. At 72 h after the treatment with the appropriate concentrations of GLP-2, the mRNA and protein expressions of zonula occludens-1 (ZO-1), occludin and claudin-1 were increased (p<0.05). U0126, an MAPK kinase inhibitor, prevented the mRNA and protein expressions of ZO-1, occludin, claudin-1 increase induced by GLP-2 (p<0.05). In conclusion, these results indicated that GLP-2 could improve the expression of TJ proteins in weaned pigs’ jejunal epithelium, and the underlying mechanism may due to the MAPK signaling pathway.
참고문헌 (29)
- Basuroy, S., "MAPK interacts with occludin and mediates EGF-induced prevention of tight junction disruption by hydrogen peroxide", Biochem. J, 393, pp.69~77 (2006)
- Benjamin, M. A., "Glucagons-like peptide-2 enhances intestinal epithelial barrier function of both Tran cellular and Para cellular pathways in the mouse", Gut, 47, pp.112~119 (2000)
- Bruewer, M., "Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms", J. Immunol, 171, pp.6164~6172 (2003)
- Burrin, D. G., "Glucagon-like peptide 2: A nutrient-responsive gut growth factor", J. Nutr, 131, pp.709~712 (2001)
- Burrin, D. G., "GLP-2 rapidly activates divergent intracellular signaling pathways involved in intestinal cell survival and proliferation in neonatal piglets", Am. J. Physiol. Endocrinol. Metab, 292, pp.E281~E291 (2007)
- Cameron, H. L., "Stress impairs murine intestinal barrier function: improvement by glucagon-like peptide-2", J. Pharmacol. Exp. Ther, 314, pp.214~220 (2005)
- Cameron, H. L., "Glucagon-like peptide-2-enhanced barrier function reduces pathophysiology in a model of food allergy", Am. J. Physiol. Gastrointest. Liver Physiol, 284, pp.G905~G912 (2003)
- Chen, Z. Y., "Effect of glucagon-like peptide-2 on modulation of intestinal epithelium tight junction in rats with obstructive jaundice", Chi. J. Gener. Surg, 17, pp.760~763 (2008)
- Drucker, D. J, "Gut adaptation and the glucagon-like peptides", Gut, 50, pp.428~435 (2002)
- GLP-2 reduces the severity of colonic injury in a murine model of experimental colitis, "Am. J. Physiol. Gastrointest. Liver Physiol", 1999, G79~G91
- Fanning, A. S., "The tight junction protein ZO-1 establishes a link between the Tran membrane protein occludin and the actin cytoskeleton", J. Biol. Chem, 273, pp.745~753 (1998)
- Favata, M. F., "Identification of a novel inhibitor of mitogen activated protein kinas", J. Biol. Chem, 273, pp.18623~18632 (1998)
- Feldman, G., "Role for TGF-beta in cyclosporine-induced modulation of renal epithelial barrier function", J. Am. Soc. Nephrol, 18, pp.1662~1671 (2007)
- Furuse, M., "Occludin: A novel integral membrane protein localizing at tight junctions", J. Cell Biol, 123, pp.1777~1788 (1993)
- Gonzalez-Mariscal, L, "Crosstalk of tight junction components with signaling pathways", Biochim. Biophys. Acta, 1778, pp.729~756 (2008)
- Howe, K. L., "Transforming growth factor-beta regulation of epithelial tight junction proteins enhances barrier function and blocks enterohemorrhagic Escherichia coli O157:H7-induced increased permeability", Am. J. Pathol, 167, pp.1587~1597 (2005)
- Jasleen, J., "Glucagon-like peptide 2 stimulates intestinal epithelial proliferation in vitro", Digest. Dis. Sci, 47, pp.1135~1140 (2002)
- Jasleen, J., "Signaling mechanisms of glucagons-like peptide 2-induced intestinal epithelial cell proliferation", J. Surg. Res, 90, pp.13~18 (2000)
- Kansagra, K., "Total parenteral nutrition adversely affects gut barrier function in neonatal piglets", Am. J. Physiol. Gastrointest. Liver Physiol, 285, pp.G1162~G1170 (2003)
- Kato, Y., "Glucagonlike peptide-2 enhances small intestinal absorptive function and mucosal mass in vivo", J. Pediatr. Surg, 34, pp.18~21 (1999)
- Kucharzik, T., "Neutrophil transmigration in inflammatory bowel disease is associated with differential expression of epithelial intercellular junction proteins", Am. J. Pathol, 159, pp.2001~2009 (2001)
- Lipschutz, J. H., "Extracellular signal-regulated kinases 1", 2 control claudin-2 expression in Madin-Darby canine kidney strain I and II cells, 2005, pp.280, 3780~3788
- Munroe, D. G., "Prototypic G protein-coupled receptor for the intestinotrophic factor glucagon-like peptide 2", Proc. Natl. Acad. Sci. USA, 96, pp.1569~1573 (1999)
- Osek, J., "Prevalence of virulence factors of Escherichia coli strains isolated from diarrheic and healthy piglets after weaning", Vet. Microbiol, 68, pp.209~217 (1999)
- Pfaffl, M. W, "A new mathematical model for relative quantification in real time RT-PCR", Nucl. Acids Res, 29(9), pp.e45~ (2001)
- Prasad, R., "Glucagonlike peptide-2 analogue enhances intestinal mucosal mass after ischemia and reperfusion", J. Pediatr. Surg, 35, pp.357~359 (2000)
- Tsukita, S., "Multifunctional strands in tight junctions", Nat. Rev. Mol. Cell Biol, 2, pp.285~293 (2001)
- Wachtel, M., "Extracellular signal-regulated protein kinase activation during reoxygenation is required to restore ischaemia-induced endothelial barrier failure", Biochem. J, 367, pp.873~879 (2002)
- Yusta, B., "Identification of glucagons-like peptide-2 (GLP-2) activated signaling pathways in baby hamster kidney fibroblasts expressing the rat GLP-2 receptor", J. Biol. Chem, 274, pp.30459~30467 (1999)
