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      Integrins Were Involved in Soybean Agglutinin Induced Cell Apoptosis in IPEC-J2

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          Abstract

          Soybean agglutinin (SBA), is a non-fiber carbohydrate related protein and a major anti-nutritional factor. Integrins, transmembrane glycoproteins, are involved in many biological processes. Although recent work suggested that integrins are involved in SBA-induced cell-cycle alterations, no comprehensive study has reported whether integrins are involved in SBA-induced cell apoptosis (SCA) in IPEC-J2. The relationship between SBA and integrins are still unclear. We aimed to elucidate the effects of SBA on IPEC-J2 cell proliferation and cell apoptosis; to study the roles of integrins in IPEC-J2 normal cell apoptosis (NCA) and SCA; and to illustrate the relationship and connection type between SBA and integrins. Thus, IPEC-J2 cells were treated with SBA at the levels of 0, 0.125, 0.25, 0.5, 1.0 or 2.0 mg/mL to determine cell proliferation and cell apoptosis. The cells were divided into control, SBA treated groups, integrin inhibitor groups, and SBA + integrin inhibitor groups to determine the integrin function in SCA. The results showed that SBA significantly ( p < 0.05) lowered cell proliferation and induced cell apoptosis in IPEC-J2 ( p < 0.05). Inhibition of any integrin type induced the cell apoptosis ( p < 0.05) and these integrins were involved in SCA ( p < 0.05). Even SBA had no physical connection with integrins, an association was detected between SBA and α-actinin-2 ACTN2 (integrin-binding protein). Additionally, SBA reduced the mRNA expression of integrins by down regulating the gene expression level of ACTN2. We concluded an evidence for the anti-nutritional mechanism of SBA by ACTN2 with integrins. Further trials are needed to prove whether ACTN2 is the only protein for connecting SBA with integrin.

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          Most cited references35

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          Signalling pathways linking integrins with cell cycle progression.

          Integrins are adhesion receptors that allow cells to sense and respond to microenvironmental signals encoded by the extracellular matrix. They are crucial for the adhesion, survival, proliferation, differentiation and migration of most cell types. In cell cycle regulation, integrin-mediated signals from the local niche constitute a spatial checkpoint to allow cells to progress from G1 to S phase, and are as important as temporal growth factor signals. Proliferation is altered in diseases such as cancer and fibrosis, so understanding how integrins contribute to this process will provide novel strategies for therapy. Here we consider recent studies to elucidate mechanisms of integrin-dependent cell cycle progression and discuss perspectives for future study. © 2013. Published by Elsevier B.V. All rights reserved.
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            Beta4 integrin is required for hemidesmosome formation, cell adhesion and cell survival

            The integrin heterodimer alpha 6 beta 4 is expressed in many epithelia and in Schwann cells. In stratified epithelia, alpha 6 beta 4 couple with BPAG1-e and BPAG2 to form hemidesmosomes, attaching externally to laminin and internally to the keratin cytoskeleton. To explore the function of this atypical integrin, and its relation to conventional actin-associated integrins, we targeted the removal of the beta 4 gene in mice. Tissues that express alpha 6 beta 4 are grossly affected. Stratified tissues are devoid of hemidesmosomes, display only a very fragile attachment to the basal lamina, and exhibit signs of degeneration and tissue disorganization. Simple epithelia which express alpha 6 beta 4 are also defective in adherence, even though they do not form hemidesmosomes. In the absence of beta 4, alpha 6 is dramatically downregulated, and other integrins do not appear to compensate for the loss of this heterodimer. These data have important implications for understanding integrin function in cell-substratum adhesion, cell survival and differentiation, and for understanding the role of alpha 6 beta 4 in junctional epidermolysis bullosa, an often lethal human disorder with pathology similar to our mice.
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              Integrin signaling in epithelial cells.

              Although most cells of adult mammals express multiple different integrins, particular types of cells have a characteristic repertoire of integrin expression. Benign and malignant epithelial cells use specific integrins to allow the epithelial microenvironment to modulate a wide variety of cell functions, including cell survival, proliferation, morphogenesis, differentiation, motility, invasion and metastasis. An important concept emerging from the data on integrin signal transduction is that integrin signaling impinges on pathways downstream of other receptors, creating elaborate intracellular signaling networks. This review highlights signal transduction functions of epithelial integrins, with particular emphasis on signaling pathways underlying some of the most important functions of epithelium.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                16 February 2018
                February 2018
                : 19
                : 2
                : 587
                Affiliations
                [1 ]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, Changchun 130118, China; panli0628@ 123456126.com (L.P.); zhaoyuan4CL52@ 123456126.com (Y.Z.); baonan203@ 123456163.com (N.B.); cagewang@ 123456163.com (T.W.)
                [2 ]Department of Animal Production, Faculty of Agriculture, Al-Azhar University, Nasr City, Cairo 11884, Egypt
                Author notes
                Article
                ijms-19-00587
                10.3390/ijms19020587
                5855809
                29462933
                001342fc-9040-47de-8a43-362a31370618
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 27 December 2017
                : 09 February 2018
                Categories
                Article

                Molecular biology
                anti-nutritional mechanism,biological functions,cell apoptosis,integrin,soybean agglutinin

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