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首页> 外文期刊>Cellular Physiology and Biochemistry >Alpha integrin subunits regulate human (Caco-2) intestinal epithelial proliferation and phenotype
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Alpha integrin subunits regulate human (Caco-2) intestinal epithelial proliferation and phenotype

机译：α整合素亚基调节人（Caco-2）肠上皮增殖和表型

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Background/Aims: Cell-matrix interactions influence intestinal epithelial biology, but the whether specific integrin heterodimers exert different effects is unclear. Methods: We used functional antibodies to investigate effects of the alpha 2, alpha 3, alpha 5, and alpha 6 integrin subunits on proliferation and differentiation of human intestinal Caco-2 cells on laminin. Cells seeded onto laminin-coated inserts in defibronectinized medium were treated with functional antibodies or normal IgG for 72 hrs and proliferation, alkaline phosphatase and dipeptidyl dipeptidase specific activity were measured. Results: Caco-2 adhesion to antibody to each alpha-integrin subunit stimulated tyrosine phosphorylation of Focal Adhesion Kinase and paxillin, suggesting that these antibodies intiate integrin-related tyrosine signalling. Proliferation was inhibited by anti-alpha 2 and anti- alpha 3, but stimulated by anti- alpha 6. Alkaline phosphatase and dipeptidyl dipeptidase specific activity were promoted by alpha 2 blockade but decreased after alpha 6 blockade. Proliferative blockade using mitomycin C or hydroxyurea prevented the effects of alpha 2 ligation on differentiation, but the decrease in alkaline phosphatase specific activity observed after alpha 6 integrin subunit blockade was preserved even after proliferative blockade. Conclusion: Integrin heterodimers modulate human Caco-2 intestinal epithelial biology on laminin in an alpha-subunit specific manner. The different effects of anti-alpha 2 and anti- alpha 6 may reflect competitition by these antibodies with integrin subunit interactions with laminin as well as initiation of their own signals or different functions for the alpha 6 integrin subunit. Copyright (C) 2000 S. Karger AG, Basel. [References: 75]
机译：背景/目的：细胞-基质相互作用会影响肠道上皮生物学，但具体的整联蛋白异二聚体是否发挥不同作用尚不清楚。方法：我们使用功能性抗体来研究α2，α3，α5和α6整联蛋白亚基对层粘连蛋白对人肠道Caco-2细胞增殖和分化的影响。将在去纤连蛋白培养基中接种到层粘连蛋白包被的插入片段上的细胞用功能性抗体或正常IgG处理72小时，并测量增殖，碱性磷酸酶和二肽基二肽酶的比活性。结果：Caco-2对每个α-整联蛋白亚基抗体的粘附刺激了局灶性粘附激酶和paxillin的酪氨酸磷酸化，表明这些抗体引发了整联蛋白相关的酪氨酸信号转导。抗α2和抗α3抑制增殖，但抗α6刺激增殖。碱性磷酸酶和二肽基二肽酶的比活性被α2阻断促进，但在α6阻断后降低。使用丝裂霉素C或羟基脲进行的增殖性阻断阻止了α2连接对分化的影响，但是即使在增殖性阻断后，α6整联蛋白亚基阻断后观察到的碱性磷酸酶比活性的降低也得以保留。结论：整联蛋白异二聚体以α-亚基特异性方式调节层粘连蛋白上的人Caco-2肠上皮生物学。抗α2和抗α6的不同作用可能反映了这些抗体与整合素亚基与层粘连蛋白的相互作用以及它们自己的信号或针对α6整合素亚基的不同功能的竞争。版权所有（C）2000 S.Karger AG，巴塞尔。 [参考：75]

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