细胞信号转导文献7.pdfVIP

Cellular Signalling 12 (2000) 435–445 /locate/cellsig Review Article Mechanical stress-initiated signal transductions in vascular smooth muscle cells Chaohong Li, Qingbo Xu* Institute for Biomedical Aging Research, Austrian Academy of Sciences, A-6020 Innsbruck, Austria Received 15 March 2000; accepted 9 May 2000 Abstract Mechanical force is an important modulator of cellular morphology and function in a variety of tissues, and is particularly important in cardiovascular systems. Vascular smooth muscle cell (VSMC) hypertrophy and proliferation contribute to the development of atherosclerosis, hypertension, and restenosis, where mechanical forces are largely disturbed. How VSMCs sense and transduce the extracellular mechanical signals into the cell nucleus resulting in quantitative and qualitative changes in gene expression is an interesting and important research field. Recently, it has been demonstrated that mechanical stress rapidly induced phosphorylation of platelet-derived growth factor (PDGF) receptor, activation of integrin receptor, stretch-activated cation channels, and G proteins, which might serve as mechanosensors. Once mechanical force is sensed, protein kinase C and mitogen-activated protein kinases (MAPKs) were activated, leading to increased c-fos and c-jun gene expression and enhanced transcription factor AP-1 DNA-binding activity. Interestingly, physical forces also rapidly resulted in expression of MAPK phosphatase-1 (MKP-1), which inactivates MAPKs. Thus, mechani