O76	The cytoskeletal protein zyxin is a mechano-sensitive signal transducer in vascular smooth muscle cells.
A.Wójtowicz, M.Hecker, M.Cattaruzza
Institute for Physiology and Pathophysiology, Heidelberg, DE.

Background: Laplace wall tension deforming medial smooth muscle cells (SMC) is a major stimulus for vascular remodelling. Initial events from mechano-sensing to nuclear signal transduction in affected SMC are poorly understood. Cytoskeletal proteins such as the focal adhesion contact (FA) protein zyxin, however, might play a crucial role in this process. Methods: Human aortic SMC (passage 2-3) were cultured on flexible membranes and subjected to cyclic stretch (3-9% elongation, 0.15 Hz at 50% time intervals for 0.5-6 h). For functional experiments, zyxin expression was suppressed with a specific anti-sense oligonucleotide prior to the onset of the stretch protocol. Analytical methods used were real time RT-PCR, Western blot and immunofluorescence analysis (IFA). Results: In quiescent SMC zyxin is localized in FA. Only upon exposure to increases in cyclic wall tension (10 min to 6 h) zyxin starts to cycle between FA, stress fibres and the nucleus. At the functional level, expression of several stretch-induced gene products (endothelin B-type receptor, tenascin-C, cyclooxygenase-1 and PAI-1) is differentially affected by nuclear translocation of zyxin, indicating that indeed zyxin acts at the transcriptional level. Conclusion: To our knowledge, zyxin is the first specific mechanotransducer modulating gene expression identified so far.

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