Integrin α8β1-fibronectin interactions promote cell survival via PI3 kinase pathway

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.