CELL REMODELING BY MECHANICAL STIMULI : ROLE OF FOVAL ADHESION MOLECULES IN POLARITY FORMATION

Endothelial Cells展示了类似纺锤形的形状，使其长度平行线与容器运行。这种明显的形状和对齐是非常重要的，可以防止细胞从血液流动中剥离。However， Cultured Endothelial Cells不能显示这样的形状和对齐。这是众所周知的，因为细胞上的机械压力，就像脉冲性血液流动的周期性循环拉伸一样，这就足够了，足以让它成为一种内皮细胞形态学。它还提出了关于细胞基素和粘合剂分子对这种形态产生的贡献的建议。The altimate goal of this project is to elucidate the intracellular signaling cascade in the stretch induced morphogenesis in cultured endothelial cells and to understand the molecular Mechanism underlying the formation of two dimensional polarity in the cell。使用Ca-D12 + Ca-D1成像，贴片钳，生物化学和分子生物技术，我们可以确定主要信号级联为以下： < uniaxial Periodic Stretch ... More → activation of SA channels→ intracellular Ca-mobilization→activation of tyrosine kinase， src，→tyrosine phosphorylation of adhesion proteins→ reorganization of stress fibers and forcal adhesion→ morphological change>。在目前的研究中，我们专注于细胞极化的起源，并获得了以下结果。： 1） As the stretch activated intracellular CaイイD12+イエD1 increase was spatially uniform， this may not be true cause of the cell polarity。（2） Stretch Dependent cAMP increase may not directly relate to the morphological change。（3）在另一边，压力纤维倾向于使拉伸轴相对于形态变化的主要方向。4）因此，可能会有另一种有信号的机制从整合中流出，在任何机制力量被直接植入，进入细胞凯尔特人。5）为了调查整合蛋白的作用，我们开发了一个近场显微镜系统，我们可以通过该系统可视化整合蛋白分子在实时中的动态。（6）集成蛋白分子被发现比我们预期的要快得多。We speculate that the signaling mManagement ism via Oracle rins along with the CaイイD12+イエD1 signaling mManagement ism may contribute to the Oracle of the cell polarity。下一个目标是我们的研究应该证明这一假说。Less（低）

Endothelial cells exhibit spindle like shape aligning their longitude parallel with vessel running. This peculiar shape and alignment is significant to prevent the cells from being pealed off by blood flow. However, cultured endothelial cells do not show such a shape and alignment. It is known that mechanical stresses onto the cells, like periodic circumferential stretch by pulsative blood flow, is enough to induce such a morphology of endothelial cells. It has been also suggested that cytoskeletons and adhesion molecules contribute to this morphogenesis. The altimate goal of this project is to elucidate the intracellular signaling cascade in the stretch induced morphogenesis in cultured endothelial cells and to understand the molecular mechanism underlying the formation of two dimensional polarity in the cell. Using Ca ィイD12+ィエD1 imaging, patch clamp, biochemical and molecular biological techniques, we could identify the major signaling cascade as follows : < uniaxial periodic stretch … More → activation of SA channels→ intracellular Ca-mobilization→activation of tyrosine kinase, src,→tyrosine phosphorylation of adhesion proteins→ reorganization of stress fibers and forcal adhesion→ morphological change>. In the present study, we focused on the origin of the cell polarity and obtained following results. : 1) As the stretch activated intracellular CaィイD12+ィエD1 increase was spatially uniform, this may not be true cause of the cell polarity. 2) Stretch dependent cAMP increase may not directly relate to the morphological change. 3) On the other hand, stress fibres tend to align perpendiculary to the stretch axis prior to the morphological change. 4) Therefore, there may be another signaling mechanism flowing from the integrin, upon which mechanical forces are directly imposed, to cytoskeletons. 5) To investigate the role of the integrin, we developed a near field microscope system by which we can visualize the dynamics of integrin molecules in real time. 6) Integrin molecules were found to be translocated rapidly than we expected. We speculate that the signaling mechanism via integrins along with the CaィイD12+ィエD1 signaling mechanism may contribute to the formation of the cell polarity. Next aim of our study should be to prove this hypothesis. Less