Survivin expression induced by endothelin-1 promotes myofibroblast resistance to apoptosis

摘要: Fibrosis of the lungs and other organs is characterized by accumulation myofibroblasts, effectors wound-repair that are responsible for deposition organization new extracellular matrix (ECM) in response to tissue injury. During resolution phase normal wound repair, myofibroblast apoptosis limits continued ECM. Mounting evidence suggests myofibroblasts from fibrotic wounds acquire resistance apoptosis, but mechanisms regulating this have not been fully elucidated. Endothelin-1 (ET-1), a soluble peptide strongly associated with fibrogenesis, decreases susceptibility through activation phosphatidylinositol 3′-OH kinase (PI3K)/AKT. Focal adhesion (FAK) also promotes PI3K/AKT-dependent – independent mechanisms, although role FAK ET-1 mediated has explored. The goal study was investigate whether contributes examine potential downstream PI3K/AKT which regulates survival. Here, we show survival Rho/ROCK-dependent FAK. anti-apoptotic actions are, turn, dependent on subsequent increased expression Survivin, member inhibitor protein (IAP) family. Collectively, these studies define novel mechanism upregulation Survivin.