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Effect of Glucagon-like Peptide 2 on Tight Junction in Jejunal Epithelium of Weaned Pigs though MAPK Signaling Pathway

  • Yu, Changsong (Animal Nutrition Institute, Sichuan Agricultural University) ;
  • Jia, Gang (Animal Nutrition Institute, Sichuan Agricultural University) ;
  • Jiang, Yi (Animal Nutrition Institute, Sichuan Agricultural University) ;
  • Deng, Qiuhong (Animal Nutrition Institute, Sichuan Agricultural University) ;
  • Chen, Zhengli (College of Animal Medicine, Sichuan Agriculture University) ;
  • Xu, Zhiwen (College of Animal Medicine, Sichuan Agriculture University) ;
  • Chen, Xiaolin (Animal Nutrition Institute, Sichuan Agricultural University) ;
  • Wang, Kangning (Animal Nutrition Institute, Sichuan Agricultural University)
  • Received : 2013.09.01
  • Accepted : 2014.01.05
  • Published : 2014.05.01

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.

References

  1. Burrin, D. G., Y. Petersen, B. Stoll, and P. Sangild. 2001. Glucagon-like peptide 2: A nutrient-responsive gut growth factor. J. Nutr. 131:709-712.
  2. Basuroy, S., A. Seth, B. Elias, A. P. Naren, and R. Rao. 2006. MAPK interacts with occludin and mediates EGF-induced prevention of tight junction disruption by hydrogen peroxide. Biochem. J. 393:69-77. https://doi.org/10.1042/BJ20050959
  3. Benjamin, M. A., D. M. McKay, P. C. Yang, H. Cameron, and M. H. Perdue. 2000. Glucagons-like peptide-2 enhances intestinal epithelial barrier function of both Tran cellular and Para cellular pathways in the mouse. Gut 47:112-119. https://doi.org/10.1136/gut.47.1.112
  4. Bruewer, M., A. Luegering, T. Kucharzik, C. A. Parkos, J. L. Madara, A. M. Hopkins, and A. Nusrat. 2003. Proinflammatory cytokines disrupt epithelial barrier function by apoptosis-independent mechanisms. J. Immunol. 171: 6164-6172. https://doi.org/10.4049/jimmunol.171.11.6164
  5. Burrin, D. G., B. Stoll, X. F. Guan, L. W. Cui, X. Y. Chang, and D. Hadsell. 2007. GLP-2 rapidly activates divergent intracellular signaling pathways involved in intestinal cell survival and proliferation in neonatal piglets. Am. J. Physiol. Endocrinol. Metab. 292:E281-E291.
  6. Cameron, H. L. and M. H. Perdue. 2005. Stress impairs murine intestinal barrier function: improvement by glucagon-like peptide-2. J. Pharmacol. Exp. Ther. 314:214-220. https://doi.org/10.1124/jpet.105.085373
  7. Drucker, D. J., B. Yusta, R. P. Boushey, B. L. DeForest, and P. L. Brubaker. 1999. Human [Gly2] GLP-2 reduces the severity of colonic injury in a murine model of experimental colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 276:G79-G91.
  8. Cameron, H. L., P. C. Yang, and M. H. Perdue. 2003. Glucagon-like peptide-2-enhanced barrier function reduces pathophysiology in a model of food allergy. Am. J. Physiol. Gastrointest. Liver Physiol. 284:G905-G912. https://doi.org/10.1152/ajpgi.00231.2002
  9. Chen, Z. Y., X. S. Feng, and P. Yang. 2008. Effect of glucagon-like peptide-2 on modulation of intestinal epithelium tight junction in rats with obstructive jaundice. Chi. J. Gener. Surg. 17:760-763.
  10. Drucker, D. J. 2002. Gut adaptation and the glucagon-like peptides. Gut 50:428-435. https://doi.org/10.1136/gut.50.3.428
  11. Fanning, A. S., B. J. Jameson, L. A. Jesaitis, and J. M. Anderson. 1998. The tight junction protein ZO-1 establishes a link between the Tran membrane protein occludin and the actin cytoskeleton. J. Biol. Chem. 273:745-753.
  12. Favata, M. F., K. Y. Horiuchi, E. J. Manos, A. J. Daulerio, D. A. Stradley, W. S. Feeser, D. E. Van Dyk, W. J. Pitts, A. E. Richard, F. Hobbs, R. A. Copeland, R. L. Magolda, P. A. Scherle, and J. M. Trzaskos. 1998. Identification of a novel inhibitor of mitogen activated protein kinas. J. Biol. Chem. 273:18623-18632. https://doi.org/10.1074/jbc.273.29.18623
  13. Feldman, G., B. Kiely, N. Martin, G. Ryan, T. McMorrow, and M. P. Ryan. 2007. Role for TGF-beta in cyclosporine-induced modulation of renal epithelial barrier function. J. Am. Soc. Nephrol. 18:1662-1671. https://doi.org/10.1681/ASN.2006050527
  14. Furuse, M., T. Hirase, M. Itoh, A. Nagafuchi, S. Yonemura, S. Tsukita, and S. Tsukita. 1993. Occludin: A novel integral membrane protein localizing at tight junctions. J. Cell Biol. 123:1777-1788. https://doi.org/10.1083/jcb.123.6.1777
  15. Gonzalez-Mariscal, L., R. Tapia, and D. Chamorro. 2008. Crosstalk of tight junction components with signaling pathways. Biochim. Biophys. Acta 1778:729-756. https://doi.org/10.1016/j.bbamem.2007.08.018
  16. Kansagra, K., B. Stoll, C. Rognerud, H. Niinikoski, N. O. Ching, R. Harvey, and D. Burrin. 2003. Total parenteral nutrition adversely affects gut barrier function in neonatal piglets. Am. J. Physiol. Gastrointest. Liver Physiol. 285:G1162-G1170. https://doi.org/10.1152/ajpgi.00243.2003
  17. Howe, K. L., C. Reardon, A. Wang, A. Nazli, and D. M. McKay. 2005. 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. 167:1587-1597. https://doi.org/10.1016/S0002-9440(10)61243-6
  18. Jasleen, J., S. W. Ashley, N. Shimoda, M. J. Zinner, and E. E. Whang. 2002. Glucagon-like peptide 2 stimulates intestinal epithelial proliferation in vitro. Digest. Dis. Sci. 47:1135-1140. https://doi.org/10.1023/A:1015062712767
  19. Jasleen, J., N. Shimoda, E. R. Shen, A. Tavakkolizadeh, E. E. Whang, D. O. Jacobs, M. J. Zinner, and S. W. Ashley. 2000. Signaling mechanisms of glucagons-like peptide 2-induced intestinal epithelial cell proliferation. J. Surg. Res. 90:13-18. https://doi.org/10.1006/jsre.2000.5818
  20. Kato, Y., D. Yu, and M. Z. Schwartz. 1999. Glucagonlike peptide-2 enhances small intestinal absorptive function and mucosal mass in vivo. J. Pediatr. Surg. 34:18-21. https://doi.org/10.1016/S0022-3468(99)90221-X
  21. Kucharzik, T., S. V. Walsh, and J. Chen. 2001. Neutrophil transmigration in inflammatory bowel disease is associated with differential expression of epithelial intercellular junction proteins. Am. J. Pathol. 159: 2001-2009. https://doi.org/10.1016/S0002-9440(10)63051-9
  22. Lipschutz, J. H., S. Li, A. Arisco, and D. F. Balkovetz. 2005. Extracellular signal-regulated kinases 1/2 control claudin-2 expression in Madin-Darby canine kidney strain I and II cells. J. Biol. Chem. 280:3780-3788. https://doi.org/10.1074/jbc.M408122200
  23. Prasad, R., K. Alavi, and M. Z. Schwartz. 2000. Glucagonlike peptide-2 analogue enhances intestinal mucosal mass after ischemia and reperfusion. J. Pediatr. Surg. 35:357-359. https://doi.org/10.1016/S0022-3468(00)90040-X
  24. Munroe, D. G., A. K. Gupta, F. Kooshesh, T. B. Vyas, G. Rizkalla, H. Wang, L. Demchyshyn, Z. J. Yang, R. K. Kamboj, H. Chen, K. McCallum, M. Sumner-Smith, D. J. Drucker, and A. C. Prototypic. 1999. Prototypic G protein-coupled receptor for the intestinotrophic factor glucagon-like peptide 2. Proc. Natl. Acad. Sci. USA 96:1569-1573. https://doi.org/10.1073/pnas.96.4.1569
  25. Osek, J. 1999. Prevalence of virulence factors of Escherichia coli strains isolated from diarrheic and healthy piglets after weaning. Vet. Microbiol. 68:209-217. https://doi.org/10.1016/S0378-1135(99)00109-1
  26. Pfaffl, M. W. 2001. A new mathematical model for relative quantification in real time RT-PCR. Nucl. Acids Res. 29 (9):e45. https://doi.org/10.1093/nar/29.9.e45
  27. Tsukita, S., M. Furuse, and M. Itoh. 2001. Multifunctional strands in tight junctions. Nat. Rev. Mol. Cell Biol. 2:285-293. https://doi.org/10.1038/35067088
  28. Wachtel, M., K. Frei, E. Ehler, C. Bauer, M. Gassmann, and S. M. Gloor. 2002. Extracellular signal-regulated protein kinase activation during reoxygenation is required to restore ischaemia-induced endothelial barrier failure. Biochem. J. 367: 873-879. https://doi.org/10.1042/BJ20020746
  29. Yusta, B., R. Somwar, F. Wang, D. Munroe, S. Grinstein, A. Klip, and D. J. Drucker. 1999. 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. 274:30459-30467. https://doi.org/10.1074/jbc.274.43.30459

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