JOURNAL BROWSE
Search
Advanced SearchSearch Tips
The Effects of Glucagon-like Peptide-2 on the Tight Junction and Barrier Function in IPEC-J2 Cells through Phosphatidylinositol 3-kinase-Protein Kinase B-Mammalian Target of Rapamycin Signaling Pathway
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
 Title & Authors
The Effects of Glucagon-like Peptide-2 on the Tight Junction and Barrier Function in IPEC-J2 Cells through Phosphatidylinositol 3-kinase-Protein Kinase B-Mammalian Target of Rapamycin Signaling Pathway
Yu, Changsong; Jia, Gang; Deng, Qiuhong; Zhao, Hua; Chen, Xiaoling; Liu, Guangmang; Wang, Kangning;
  PDF(new window)
 Abstract
Glucagon-like peptide-2 (GLP-2) is important for intestinal barrier function and regulation of tight junction (TJ) proteins, but the intracellular mechanisms of action remain undefined. The purpose of this research was to determine the protective effect of GLP-2 mediated TJ and transepithelial electrical resistance (TER) in lipopolysaccharide (LPS) stressed IPEC-J2 cells and to test the hypothesis that GLP-2 regulate TJ and TER through the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling pathway in IPEC-J2 cells. Wortmannin and LY294002 are specific inhibitors of PI3K. The results showed that LPS stress decreased TER and TJ proteins occludin, claudin-1 and zonula occludens protein 1 (ZO-1) mRNA, proteins expressions (p<0.01) respectively. GLP-2 (100 nmol/L) promote TER and TJ proteins occludin, claudin-1, and zo-1 mRNA, proteins expressions in LPS stressed and normal IPEC-J2 cells (p<0.01) respectively. In normal cells, both wortmannin and LY294002, PI3K inhibitors, prevented the mRNA and protein expressions of Akt and mTOR increase induced by GLP-2 (p<0.01) following with the significant decreasing of occludin, claudin-1, ZO-1 mRNA and proteins expressions and TER (p<0.01). In conclusion, these results indicated that GLP-2 can promote TJ`s expression and TER in LPS stressed and normal IPEC-J2 cells and GLP-2 could regulate TJ and TER through the PI3K/Akt/mTOR pathway.
 Keywords
Glucagon-like Peptide-2;IPEC-J2 Cell;Tight Junction;Transepithelial Electrical Resistance;Phosphatidylinositol 3-Kinase-Akt-mTOR Signaling Pathway;
 Language
English
 Cited by
 References
1.
Agresti, A. and M. Kateri. 2011. Categoricaldata analysis. Springer Berlin Heidelberg, Berlin, Germany.

2.
Arce, C., M. Ramirez-Boo, C. Lucena, and J. J. Garrido. 2010. Innate immune activation of swine intestinal epithelial cell lines (IPEC-J2 and IPI-2I) in response to LPS from Salmonella typhimurium. Comp. Immunol. Microbiol. Dis. 33:161-174. crossref(new window)

3.
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. crossref(new window)

4.
Cheeseman, C. I. 1997. Upregulation of SGLT-1 transport activity in rat jejunum induced by GLP-2 infusion in vivo. Am. J. Physiol. Regul. Integr. Comp. Physiol. 273:R1965-R1971.

5.
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. Chin. J. Gen. Surg. 17:760-763.

6.
Dong, C. X., W. Zhao, C. Solomon, K. J. Rowland, C. Ackerley, S. Robine, and P. L. Brubaker. 2013. The intestinal epithelial insulin-like growth factor-1 receptor links glucagon-like peptide-2 action to gut barrier function. Endocrinology 155:370-379.

7.
Geens, M. M. and T. A. Niewold. 2010. Preliminary characterization of the transcriptional response of the porcine intestinal cell line IPEC-J2 to enterotoxigenic Escherichia coli, Escherichia coli, and E. coli lipopolysaccharide. Comp. Funct. Genomics 2010: Article ID 469583.

8.
Guo, S., R. Al-Sadi, H. M. Said, and T. Y. Ma. 2013. Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14. Am. J. Pathol. 182:375-387. crossref(new window)

9.
Gonzalez-Mariscal, L., R. Tapia, and D. Chamorro. 2008. Crosstalk of tight junction components with signaling pathways. Biochem. Biophys. Acta-Biomembranes 1778:729-756. crossref(new window)

10.
Hu, C. H., K. Xiao, Z. S. Luan, and J. Song. 2013. Early weaning increases intestinal permeability, alters expression of cytokine and tight junction proteins, and activates mitogen-activated protein kinases in pigs. J. Anim. Sci. 91:1094-1101. crossref(new window)

11.
Hou, Y., L. Wang, W. Zhang, Z. Yang, B. Ding, H. Zhu, and G. Wu. 2012. Protective effects of N-acetylcysteine on intestinal functions of piglets challenged with lipopolysaccharide. Amino Acids 43:1233-1242. crossref(new window)

12.
Koehler, J. A., W. Harper, M. Barnard, B. Yusta, and D. J. Drucker. 2008. Glucagon-like peptide-2 does not modify the growth or survival of murine or human intestinal tumor cells. Cancer Res. 68:7897-7904. crossref(new window)

13.
Li. Q., Y. Liu, Z. Che, H. Zhu, G. Meng, Y. Hou, and F. Chen. 2012. Dietary L-arginine supplementation alleviates liver injury caused by Escherichia coli LPS in weaned pigs. Innate Immun. 18:804-814. crossref(new window)

14.
Liu, Y., J. Huang, Y. Hou, H. Zhu, S. Zhao, B. Ding, and W. Fan. 2008. Dietary arginine supplementation alleviates intestinal mucosal disruption induced by Escherichia coli lipopolysaccharide in weaned pigs. Br. J. Nutr. 100:552-560. crossref(new window)

15.
Moran, G. W., C. O'Neill, and J. T. McLaughlin. 2012. GLP-2 enhances barrier formation and attenuates $TNF{\alpha}$-induced changes in a Caco-2 cell model of the intestinal barrier. Regul. Pept. 178:95-101. crossref(new window)

16.
Naimi, R. M., K. B. Madsen, C. Askov-Hansen, C. F. Brandt, B. Hartmann, J. J. Holst, and P. B. Jeppesen. 2013. A doseequivalent comparison of the effects of continuous subcutaneous glucagon-like peptide 2 (GLP-2) infusions versus meal related GLP-2 injections in the treatment of short bowel syndrome (SBS) patients. Regul. Pept. 184:47-53. crossref(new window)

17.
Niessen, C. M. and C. J. Gottardi. 2008. Molecular components of the adherens junction. Biochem. Biophys. Acta-Biomembranes 1778:562-571. crossref(new window)

18.
Paszti-Gere, E., G. Matis, O. Farkas, A. Kulcsar, O. Palocz, G. Csiko, and P. Galfi. 2014. The effects of intestinal LPS exposure on inflammatory responses in a porcine enterohepatic co-culture system. Inflammation 37:247-260. crossref(new window)

19.
Pfaffl, M. W. 2001. A new mathematical model for relative quantification in real time RT-PCR. Nucl. Acids Res. 29:e45. crossref(new window)

20.
Razzuoli, E., R. Villa, and M. Amadori. 2013. IPEC-J2 cells as reporter system of the anti-inflammatory control actions of interferon-alpha. J. Interferon. Cytokine Res. 33:597-605. crossref(new window)

21.
Smith, F., J. E. Clark, B. L. Overman, C. C. Tozel, J. H. Huang, J. E. Rivier, and A. J. Moeser. 2010. Early weaning stress impairs development of mucosal barrier function in the porcine intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 298:G352-G363. crossref(new window)

22.
Sigalet, D. L., E. de Heuvel, L. Wallace, E. Bulloch, J. Turner, P. Nation, and J. J. Holst. 2014. Effects of chronic glucagon-like peptide-2 therapy during weaning in neonatal pigs. Regul. Pept. 188:70-80. crossref(new window)

23.
Shi, X., F. Zhou, X. Li, B. Chang, D. Li, Y. Wang, and X. Guan. 2013. Central GLP-2 enhances hepatic insulin sensitivity via activating PI3K signaling in POMC neurons. Cell Metabol. 18:86-98. crossref(new window)

24.
Shi, X., X. Li, Y. Wang, K. Zhang, F. Zhou, L. Chan, and X. Guan. 2011. Glucagon-like peptide-2-stimulated protein synthesis through the PI 3-kinase-dependent Akt-mTOR signaling pathway. Am. J. Physiol. Endocrinol. Metab. 300:E554-E563. crossref(new window)

25.
Thymann, T., I. Le Huërou-Luron, Y. M. Petersen, M. S. Hedemann, J. Elinf, B. B. Jensen, and P. T. Sangild. 2014. Glucagon-like peptide 2 treatment may improve intestinal adaptation during weaning. J. Anim. Sci. 92:2070-2079. crossref(new window)

26.
Wijtten, P. J., J. van der Meulen, and M. W. Verstegen. 2011. Intestinal barrier function and absorption in pigs after weaning: A review. Br. J. Nutr. 105:967-981. crossref(new window)

27.
Yusta, B., J. Estall, and D. J. Drucker. 2002. Glucagon-like peptide-2 receptor activation engages bad and glycogen synthase kinase-3 in a protein kinase A-dependent manner and prevents apoptosis following inhibition of phosphatidylinositol 3-kinase. J. Biol. Chem. 27:24896-24906.

28.
Zhao, Y., G. Qin, Z. Sun, D. Che, N. Bao, and X. Zhang. 2011. Effects of soybean agglutinin on intestinal barrier permeability and tight junction protein expression in weaned piglets. Int. J. Mol. Sci. 12:8502-8512. crossref(new window)