Integrin α8β1-fibronectin interactions promote cell survival via PI3 kinase pathway
Integrin α8β1-fibronectin interactions promote cell survival via PI3 kinase pathway
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DOI：
10.1016/j.bbrc.2005.01.125
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发表时间：
2005-04-01
影响因子：
3.1
通讯作者：
Schnapp, LM
中科院分区：
文献类型：
--
作者：
Farias, E;Lu, M;Schnapp, LM
整合素信号在正常生长、分化和损伤反应的许多方面起着关键作用。在成人中，α8β1在肺泡肌成纤维细胞中表达，并在肺纤维化和其他器官损伤模型中上调。损伤后，产生纤维连接蛋白的肌成纤维细胞的存活是纤维化发展的重要决定因素。利用稳定的α-8转基因细胞系，我们发现在血清剥夺期间，α-β1与其配体纤维连接蛋白的相互作用促进了细胞的存活。纤维连接蛋白黏附后激活了包括P13和MAP在内的多条细胞信号转导通路。然而，P13激酶抑制剂LY294002可阻断α8介导的细胞存活，而蛋白激酶C抑制剂星形孢子素或丝裂原活化蛋白激酶抑制剂PD98059则不能阻断该作用。P13激酶的显性负性结构也抑制了α8介导的细胞存活。因此。Alpha8介导的存活似乎是由P13激酶途径介导的。表达A8的肌成纤维细胞的存活可能有助于损伤后的持续性纤维化。(C)2005 Elsevier Inc.保留所有权利。
Integrin signaling plays a critical role in many aspects of normal growth, differentiation, and injury response. In the adult, alpha8beta1 is expressed in alveolar myofibroblasts and is upregulated in pulmonary fibrosis and other models of organ injury. Following injury, survival of fibronectin-producing myofibroblasts cells is an important determinant of development of fibrosis. Using stable alpha8-transfected cell lines, we show that interactions of a8betal with its ligand, fibronectin, promote cell survival during serum deprivation. Multiple cell signaling pathways were activated following fibronectin adhesion, including P13 kinase and MAP kinase. However, the alpha8-mediated cell survival was blocked by LY294002, a P13 kinase inhibitor, but not by staurosporine, a PKC inhibitor, or PD98059, a MAPK kinase inhibitor. A dominant negative construct of P13 kinase also inhibited alpha8-mediated cell survival. Therefore. alpha8-mediated survival appears to be mediated by the P13 kinase pathway. Survival of a8-expressing myofibroblasts may contribute to persistent fibrosis following injury. (C) 2005 Elsevier Inc. All rights reserved.