Browse > Article
http://dx.doi.org/10.14348/molcells.2017.2207

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)
Publication Information
Molecules and Cells / v.40, no.2, 2017 , pp. 109-116 More about this Journal
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
cell cycle; cell proliferation; functional mechanism; integrin subunits; soybean agglutinin;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Cox, D., Brennan, M., and Moran, N. (2010). Integrins as therapeutic targets: lessons and opportunities. Nat. Rev. Drug. Discov. 9, 804-820.   DOI
2 De Arcangelis, A., and Georges-Labouesse, E. (2000) Integrin and ECM functions: roles in vertebrate development. Trends Genet. 16, 389-395.   DOI
3 Derheimer, F.A., and Kastan, M.B. (2010). Multiple roles of ATM in monitoring and maintaining DNA integrity. FEBS Lett. 584, 3675-3681.   DOI
4 Giancotti, F.G. (1997). Integrin signaling: specificity and control of cell survival and cell cycle progression. Curr. Opin. Cell Biol. 9, 691-700.   DOI
5 Gilcrease, M.Z. (2007). Integrin signaling in epithelial cells. Cancer Lett. 247, 1-25.   DOI
6 Grant, G. (1989). Antinutritional effects of soybean: A Review. Prog. Food Nutr. Sci. 13, 317-348.
7 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.   DOI
8 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.   DOI
9 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.
10 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.   DOI
11 Burke, R.D. (1999). Invertebrate integrins: structure, function, and evolution. Int. Rev. Cytol. 191, 257-284.
12 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.   DOI
13 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.   DOI
14 Barczyk, M., Carracedo, S., and Gullberg, D. (2010). Integrins. Cell. Tissue Res. 339, 269-280.   DOI
15 Beaulieu, J.F. (1997). Extracellular matrix components and integrins in relationship to human intestinal epithelial cell differentiation. Prog. Histochem. Cytochem. 31, 1-78.
16 Beaulieu, J.F. (1999). Integrins and human intestinal cell functions. Front. Biosci. 4, 310-320.   DOI
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.   DOI
18 Malik, M., Segars, J., and Catherino, W.H. (2012). Integrin ${\beta}1$ regulates leiomyoma cytoskeletal integrity and growth. Matrix Biol. 31, 389-397.   DOI
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.   DOI
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.   DOI
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 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.   DOI
24 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.   DOI
25 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.   DOI
26 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.   DOI
27 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.
28 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.
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 Yau, T., Dan, X., Ng, C.C., and Ng, T.B. (2015). Lectins with potential for anti-cancer therapy. Molecules 20, 3791-810.   DOI
32 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.   DOI
33 Tervo, K., Tervo, T., van Setten, G.B., and Virtanen, I. (1991). Integrins in human corneal epithelium. Cornea 10, 461-465.   DOI
34 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.
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.   DOI
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.   DOI