Cell adhesion events mediated by alpha 4 integrins are essential in placental and cardiac development.
Cell adhesion events mediated by alpha 4 integrins are essential in placental and cardiac development.
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发表时间：
1995-02
期刊：
影响因子：
4.6
通讯作者：
Joy T. Yang;H. Rayburn;R. Hynes
中科院分区：
文献类型：
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作者：
Joy T. Yang;H. Rayburn;R. Hynes
α 4整联蛋白是细胞表面受体，其通过分别与纤连蛋白（FN）和血管细胞粘附分子1（VCAM-1）相互作用来介导细胞-细胞外基质（ECM）和细胞-细胞粘附。我们已经在α 4整合素亚基基因中产生了无效突变。纯合子无效胚胎不表达α 4整合素，并显示出两个意想不到的缺陷，这两个缺陷都导致胚胎死亡。第一个缺陷是在胎盘形成过程中尿囊与绒毛膜融合失败。第二种是心外膜和冠状血管的发展导致心脏出血。这两个过程显然涉及α 4整合素的相互作用，以前没有怀疑。α 4整联蛋白和VCAM-1在这些相互作用的位点表达。这些结果提高了针对α 4整合素的堕胎药的可能性，并对目前设计用于阻断α 4整合素在炎症中的功能的药物的潜在副作用提出了严重的问题。
alpha 4 integrins are cell surface receptors that mediate cell-extracellular matrix (ECM) and cell-cell adhesions by interacting with fibronectin (FN) and vascular cell adhesion molecule 1 (VCAM-1), respectively. We have generated a null mutation in the gene for the alpha 4 integrin subunit. Homozygous null embryos express no alpha 4 integrins and show two unexpected defects, both of which lead to embryonic lethality. The first defect is failure of fusion of the allantois with the chorion during placentation. The second is in the development of the epicardium and coronary vessels leading to cardiac hemorrhage. Both processes clearly involve alpha 4 integrin interactions that were previously unsuspected. alpha 4 integrin and VCAM-1 are expressed at the sites of these interactions. These results raise the possibility of abortifacients targeting alpha 4 integrins, and raise serious questions about potential side effects of drugs currently being designed to block alpha 4 integrin functions in inflammation.