Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

The Integrins Involved in Soybean Agglutinin-Induced Cell Cycle Alterations in IPEC-J2

  • Pan, Li (Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science, Jilin Province, College of Animal Science and Technology, Jilin Agricultural University) ;
  • Zhao, Yuan (Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science, Jilin Province, College of Animal Science and Technology, Jilin Agricultural University) ;
  • Yuan, Zhijie (Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science, Jilin Province, College of Animal Science and Technology, Jilin Agricultural University) ;
  • Farouk, Mohammed Hamdy (Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science, Jilin Province, College of Animal Science and Technology, Jilin Agricultural University) ;
  • Zhang, Shiyao (Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science, Jilin Province, College of Animal Science and Technology, Jilin Agricultural University) ;
  • Bao, Nan (Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science, Jilin Province, College of Animal Science and Technology, Jilin Agricultural University) ;
  • Qin, Guixin (Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Key Laboratory of Animal Nutrition and Feed Science, Jilin Province, College of Animal Science and Technology, Jilin Agricultural University)
  • Received : 2016.08.29
  • Accepted : 2017.01.06
  • Published : 2017.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Soybean agglutinin (SBA) is an anti-nutritional factor of soybean, affecting cell proliferation and inducing cytotoxicity. Integrins are transmembrane receptors, mediating a variety of cell biological processes. This research aims to study the effects of SBA on cell proliferation and cell cycle progression of the intestinal epithelial cell line from piglets (IPEC-J2), to identify the integrin subunits especially expressed in IPEC-J2s, and to analyze the functions of these integrins on IPEC-J2 cell cycle progression and SBA-induced IPEC-J2 cell cycle alteration. The results showed that SBA lowered cell proliferation rate as the cell cycle progression from G0/G1 to S phase (P < 0.05) was inhibited. Moreover, SBA lowered mRNA expression of cell cycle-related gene CDK4, Cyclin E and Cyclin D1 (P < 0.05). We successfully identified integrins ${\alpha}2$, ${\alpha}3$, ${\alpha}6$, ${\beta}1$, and ${\beta}4$ in IPEC-J2s. These five subunits were crucial to maintain normal cell proliferation and cell cycle progression in IPEC-J2s. Restrain of either these five subunits by their inhibitors, lowered cell proliferation rate, and arrested the cells at G0/G1 phase of cell cycle (P < 0.05). Further analysis indicated that integrin ${\alpha}2$, ${\alpha}6$, and ${\beta}1$ were involved in the blocking of G0/G1 phase induced by SBA. In conclusion, these results suggested that SBA lowered the IPEC-J2 cell proliferation rate through the perturbation of cell cycle progression. Furthermore, integrins were important for IPEC-J2 cell cycle progression, and they were involved in the process of SBA-induced cell cycle progression alteration, which provide a basis for further revealing SBA anti-proliferation and anti-nutritional mechanism.

Keywords

References

  1. Assoian, R.K., and Schwartz, M.A. (2001). Coordinate signaling by integrins and receptor tyrosine kinases in the regulation of G1 phase cell-cycle progression. Curr. Opin. Genet. Dev. 11, 48-53. https://doi.org/10.1016/S0959-437X(00)00155-6
  2. Bakke-McKellep, A.M., Sanden, M., Danieli, A., Acierno, R., Hemre, G.I., Maffia, M., and Krogdahl, A. (2008). Atlantic salmon (Salmo salar L.) parr fed genetically modified soybeans and maize: Histological, digestive, metabolic, and immunological investigations. Res. Vet. Sci. 84, 395-408. https://doi.org/10.1016/j.rvsc.2007.06.008
  3. Barczyk, M., Carracedo, S., and Gullberg, D. (2010). Integrins. Cell. Tissue Res. 339, 269-280. https://doi.org/10.1007/s00441-009-0834-6
  4. Beaulieu, J.F. (1997). Extracellular matrix components and integrins in relationship to human intestinal epithelial cell differentiation. Prog. Histochem. Cytochem. 31, 1-78.
  5. Beaulieu, J.F. (1999). Integrins and human intestinal cell functions. Front. Biosci. 4, 310-320. https://doi.org/10.2741/A429
  6. Burke, R.D. (1999). Invertebrate integrins: structure, function, and evolution. Int. Rev. Cytol. 191, 257-284.
  7. Cox, D., Brennan, M., and Moran, N. (2010). Integrins as therapeutic targets: lessons and opportunities. Nat. Rev. Drug. Discov. 9, 804-820. https://doi.org/10.1038/nrd3266
  8. De Arcangelis, A., and Georges-Labouesse, E. (2000) Integrin and ECM functions: roles in vertebrate development. Trends Genet. 16, 389-395. https://doi.org/10.1016/S0168-9525(00)02074-6
  9. Derheimer, F.A., and Kastan, M.B. (2010). Multiple roles of ATM in monitoring and maintaining DNA integrity. FEBS Lett. 584, 3675-3681. https://doi.org/10.1016/j.febslet.2010.05.031
  10. Giancotti, F.G. (1997). Integrin signaling: specificity and control of cell survival and cell cycle progression. Curr. Opin. Cell Biol. 9, 691-700. https://doi.org/10.1016/S0955-0674(97)80123-8
  11. Gilcrease, M.Z. (2007). Integrin signaling in epithelial cells. Cancer Lett. 247, 1-25. https://doi.org/10.1016/j.canlet.2006.03.031
  12. Grant, G. (1989). Antinutritional effects of soybean: A Review. Prog. Food Nutr. Sci. 13, 317-348.
  13. Hart, S.D., Bharadwa, A.S., and Brown, P.B. (2010). Soybean lectins and trypsin inhibitors, but not oligosaccharides or the interactions of factors, impact weight gain of rainbow trout (Oncorhynchus mykiss). Aquaculture 306, 310-314. https://doi.org/10.1016/j.aquaculture.2010.03.027
  14. Lee, S.T., Jang, M., Lee, G., and Lim, J.M. (2013). Development of three dimensional culture and expression of integrin heterodimers in human embryonic stem cells. Organogenesis 9, 143-148. https://doi.org/10.4161/org.25412
  15. Li, Z., Li, D., Qiao, S., Zhu, X., and Huang, C. (2003). Anti-nutritional effects of a moderate dose of soybean agglutinin in the rat. Arch. Tierernahr. 57, 267-277.
  16. Lin, G.N., Zhang, X., Ren, J., Pang, Z.M., Wang, C.H., Xu, N., and Xi, R.W. (2013). Integrin signaling is required for maintenance and proliferation of intestinal stem cells in Drosophila. Dev. Biol. 377, 177-187. https://doi.org/10.1016/j.ydbio.2013.01.032
  17. Louvard, D., Kedinger, M., and Hauri, H.P. (1992). The differentiating intestinal epithelial cell: Establishment and maintenance of functions through interactions between cellular structures. Annu. Rev. Cell. Biol. 8, 157-195. https://doi.org/10.1146/annurev.cb.08.110192.001105
  18. Malik, M., Segars, J., and Catherino, W.H. (2012). Integrin ${\beta}1$ regulates leiomyoma cytoskeletal integrity and growth. Matrix Biol. 31, 389-397. https://doi.org/10.1016/j.matbio.2012.09.005
  19. Maxwell, J.E. (2011). Soybeans: Cultivation, Uses and Nutrition. Nova Science Publishers, Inc. New York.
  20. Moreno-Layseca, P., and Streuli, C.H. (2014). Signalling pathways linking integrins with cell cycle progression. Matrix Biol. 34, 144-153. https://doi.org/10.1016/j.matbio.2013.10.011
  21. Naci, D., and Aoudjit, F. (2014). Alpha2beta1 integrin promotes T cell survival and migration through the concomitant activation of ERK/Mcl-1 and p38 MAPK pathways. Cell. Signal. 26, 2008-2015. https://doi.org/10.1016/j.cellsig.2014.05.016
  22. Ohba, H., and Bakalova, R. (2003). Relationships between degree of binding, cytotoxicity and cytoagglutinating activity of plant-derived agglutinins in normal lymphocytes and cultured leukemic cell lines. Cancer Chemother. Pharmacol. 51, 451-458.
  23. Pan, L., Qin, G.X., Zhao, Y., Wang, J., Liu, F.F., and Che, D.S. (2013). Effects of soybean agglutinin on mechanical barrier function and tight junction protein expression in intestinal epithelial cells from piglets. Int. J. Mol. Sci. 14, 21689-21704. https://doi.org/10.3390/ijms141121689
  24. Pan, L., Zhao, Y., Yuan, Z.J., and Qin, G.X. (2016). Research advances on structure and biological functions of integrins. Springerplus. 5, 1094-1105. https://doi.org/10.1186/s40064-016-2502-0
  25. Pozzi, A., and Zent, R. (2014). New insights into disorders of basement membranes and integrins of the kidney. Drug Discov. Today Dis. Models. 11, 37-44. https://doi.org/10.1016/j.ddmod.2014.07.003
  26. Pusztai, A., Ewen, S.W.B., Grant, G., Peumans, W.J., van Damme, E.J.M., Rubio, L., and Bardocz, S. (1990). Relationship between survival and binding of plant lectins during small intestinal passage and their effectiveness as growth factors. Digestion 2, 308-316.
  27. Rhoads, J.M., Chen, W., Chu, P., Berschneider, H.M., Argenzio, R.A., and Paradiso, A.M. (1994). l-Glutamine and l-asparagine stimulate $Na^+$-$H^+$ exchange in porcine jejunal enterocytes. Am. J. Physiol. 266, 828-838.
  28. Sancar, A., Lindseyboltz, L.A., Unsalkacmaz, K., and Linn, S. (2004). Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu. Rev. Biochem. 73, 39-85. https://doi.org/10.1146/annurev.biochem.73.011303.073723
  29. Soares, R., Franco, C., Pires, E., Ventosa, M., Palhinhas, R., Koci, K., de Almeida, A.M., and Coelho, A.V. (2014). Mass spectrometry and animal science: Protein identification strategies and particularities of farm animal species. J. Proteomic. 75, 4190-4206.
  30. SPSS (2010). Statistical Software Package for the Social Sciences. SPSS Inc., USA.
  31. Stepp, M.A., Spurr-Michaud, S., Tisdale, A., Elwell, J., and Gipson, I.K. (1990). ${\alpha}6{\beta}4$ integrin heterodimer is a component of hemidesmosomes. Proc. Nat. Acad. Sci. USA 87, 8970-8974. https://doi.org/10.1073/pnas.87.22.8970
  32. Tervo, K., Tervo, T., van Setten, G.B., and Virtanen, I. (1991). Integrins in human corneal epithelium. Cornea 10, 461-465. https://doi.org/10.1097/00003226-199111000-00001
  33. Vandesompele, J., DePreter, K., Pattyn, F., Poppe, B., VanRoy, N., DePaepe, A., and Speleman, F. (2002). Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 3, 1-12.
  34. Yau, T., Dan, X., Ng, C.C., and Ng, T.B. (2015). Lectins with potential for anti-cancer therapy. Molecules 20, 3791-810. https://doi.org/10.3390/molecules20033791
  35. Zhang, Y.T., Wu, D., Xia, F.J., Xian, H.Y., Zhu, X.Y., Cui, H.J., and Huang, Z.P. (2016). Downregulation of HDAC9 inhibits cell proliferation and tumor formation by inducing cell cycle arrest in retinoblastoma. Biochem. Bioph. Res. Commun. 473, 600-606. https://doi.org/10.1016/j.bbrc.2016.03.129
  36. Zhao, Y., Qin, G.X., Sun, Z.W., Che, D.S., Bao, N., and Zhang, X.D. (2011). Effects of soybean agglutinin on intestinal barrier permeability and tight junction protein expression in weaned piglets. Int. J. Mol. Sci. 12, 8502-8512. https://doi.org/10.3390/ijms12128502

Cited by

  1. The Influences of Soybean Agglutinin and Functional Oligosaccharides on the Intestinal Tract of Monogastric Animals vol.19, pp.2, 2018, https://doi.org/10.3390/ijms19020554
  2. Integrins Were Involved in Soybean Agglutinin Induced Cell Apoptosis in IPEC-J2 vol.19, pp.2, 2018, https://doi.org/10.3390/ijms19020587
  3. Differential Apoptotic and Mitogenic Effects of Lectins in Zebrafish vol.10, pp.None, 2017, https://doi.org/10.3389/fendo.2019.00356
  4. Enteroids: Promising in Vitro Models for Studies of Intestinal Physiology and Nutrition in Farm Animals vol.67, pp.9, 2017, https://doi.org/10.1021/acs.jafc.8b06908
  5. Intracellular invasion and survival of Brucella neotomae , another possible zoonotic Brucella species vol.14, pp.4, 2017, https://doi.org/10.1371/journal.pone.0213601
  6. Airway epithelial ITGB4 deficiency in early life mediates pulmonary spontaneous inflammation and enhanced allergic immune response vol.24, pp.5, 2017, https://doi.org/10.1111/jcmm.15000
  7. Regulation of Intestinal Inflammation by Soybean and Soy-Derived Compounds vol.10, pp.4, 2017, https://doi.org/10.3390/foods10040774