STRETCH-INDUCED CELL MORPHOGENEISI : MOLECULAR MECHANISM OF DIRECTIONSENSITIVITY AND POLARITY FORMATION

拉伸诱导的细胞形态发生:方向敏感性和极性形成的分子机制

基本信息

  • 批准号:
    08458206
  • 负责人:
  • 金额:
    $ 5.44万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
  • 财政年份:
    1996
  • 资助国家:
    日本
  • 起止时间:
    1996 至 1997
  • 项目状态:
    已结题

项目摘要

Endothelial cells exhibit spindle like shape aligning their longtude parallel with vessel running. This peculiar shape and alignment is isgnificant 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 shear stress and periodic circumferential stretch, by pulsative blood flow are enough to induce such a morphology in 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 signaling cascade in the stretchOinduced morphogenesis in cultured endothelial cells and to understand the molecular mechanism underlying the formation of two dimensional polarity in the cell. Using Ca^<2+>imaging, patch clamp, biochemical and molecular biological techniques, we could identify the major signaling cascade in the stretch-induced morphogenesis as follows : <uniaxial periodic stretch* activation of SA channels* intracellular C_amobilization* activation of calcinyrin* activation of tyrosine kinase, src, * tyrosine phosphorylation of adhesion proteins* reorganization of stress fibers and forcal adhesion* morphological change>. However, as the stretch activated Ca^<2+> increase was spatially uniform, this may not be the cause of the cell polarity. On the other hand, tyrosine phosphorylated proteins favored to distribute at the elongating portion of the cell. Hence, it is possible that there is another signaling mechanism flowing from adhesion plaque (integrin), upon which mechanical forces are directly imposed, to intracellular space. This mechanism may along with the former signaling mechanism contribute to the formation of the cell polarity through the regulation of tyrosine phosphorylation of focal adhesion proteins. Next step of our project should be to prove this hypothesis.
内皮细胞呈现纺锤状形状,其长度与血管运行平行。这种奇特的形状和排列对于防止细胞被血流剥离具有重要意义。然而,培养的内皮细胞并不表现出这样的形状和排列。已知脉动血流对细胞施加的机械应力,如剪切应力和周期性圆周拉伸,足以诱导内皮细胞出现这种形态。也有人认为细胞骨架和粘附分子有助于这种形态发生。该项目的最终目标是阐明在培养的内皮细胞中拉伸O诱导的形态发生中的信号级联,并了解细胞中二维极性形成的分子机制。使用Ca^2+成像、膜片钳、生化和分子生物学技术,我们可以确定拉伸诱导的形态发生中的主要信号级联反应如下:<单轴周期性拉伸* SA通道的激活*细胞内C_amobilization*钙调蛋白的激活*酪氨酸激酶的激活,src,*粘附的酪氨酸磷酸化 蛋白质* 应力纤维重组和粘连* 形态变化>。然而,由于拉伸激活的Ca 2+ 增加在空间上是均匀的,所以这可能不是细胞极性的原因。另一方面,酪氨酸磷酸化蛋白倾向于分布在细胞的伸长部分。因此,可能存在另一种信号机制,从直接施加机械力的粘附斑块(整合素)流向细胞内空间。该机制可能与前一种信号传导机制一起通过调节粘着斑蛋白的酪氨酸磷酸化来促进细胞极性的形成。我们项目的下一步应该是证明这个假设。

项目成果

期刊论文数量(32)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Qi Z., Sokabe, M.: "Dynamic properties of individual water molecules in a hydrophobic pore lined with acy1 chains: a molecular dynamics study." Biophys Chem. (in press).
Qi Z.,Sokabe,M.:“内衬 acy1 链的疏水孔中单个水分子的动态特性:分子动力学研究。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Qi Z., Sokabe, M.: "Dynamic properties of individual water molecules in a hydrophobic pore lined with acy1 chains : a moleculardynamics study." Biophys.Chem.(in press).
Qi Z.,Sokabe,M.:“内衬 acy1 链的疏水孔中单个水分子的动态特性:分子动力学研究。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Kobuke,Y.,Tanaka,Y.,Sokabe,M.: "Artificial non-peptide single ion channels." Progr Cell Res.6. 167-188 (1996)
Kobuke,Y.、Tanaka,Y.、Sokabe,M.:“人工非肽单离子通道。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Okada,H.,Yoshida,J.,Sokabe,M.,Wakabayashi,T.,Hagiwara,M.: "Suppression of CD44 expression decreases migartion and invasion of human glioma cells." Int J Cancer Res. 66. 255-260 (1996)
Okada,H.、Yoshida,J.、Sokabe,M.、Wakabayashi,T.、Hagiwara,M.:“抑制 CD44 表达可减少人胶质瘤细胞的迁移和侵袭。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Qi Z., Sokabe,M.: "Dynamic properties of individual water molecules in a hydrophobic pore lined with acyl chains : a molecular dynamics study." Biophys Chem. (in press).
Qi Z.,Sokabe,M.:“内衬酰基链的疏水孔中单个水分子的动态特性:分子动力学研究。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

SOKABE Masahiro其他文献

TRPC chanel inhibitors reduce vulnerability to atrial fibrillaion in acutely-inflated rabbit atria.
TRPC 通道抑制剂可降低兔心房急性膨胀时发生心房颤动的可能性。
  • DOI:
  • 发表时间:
    2008
  • 期刊:
  • 影响因子:
    0
  • 作者:
    YAMAMOTO Mitsuru;UEDA Norihiro;HORIBA Mitsuru;HONJO Haruo;KAMIYA Kaichiro;KODAMA Itsuo;SOKABE Masahiro
  • 通讯作者:
    SOKABE Masahiro

SOKABE Masahiro的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('SOKABE Masahiro', 18)}}的其他基金

A study on a novel therapeutic strategy for Alzheimer's disease Using neurosteroids.
使用神经类固醇治疗阿尔茨海默病的新策略的研究。
  • 批准号:
    24659259
  • 财政年份:
    2012
  • 资助金额:
    $ 5.44万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Possible roles of actomyosin and mechanosensitive channels in substrate rigidity sensing of cells
肌动球蛋白和机械敏感通道在细胞基质刚性传感中的可能作用
  • 批准号:
    24247028
  • 财政年份:
    2012
  • 资助金额:
    $ 5.44万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
A study on the novel therapeutic drugs to protect delayed neuronal death after stroke
保护脑卒中后迟发性神经元死亡的新型治疗药物的研究
  • 批准号:
    22659109
  • 财政年份:
    2010
  • 资助金额:
    $ 5.44万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Actin filaments work as a negative tension sensor: elucidation of itsphysiochemical mechanism
肌动蛋白丝作为负张力传感器:阐明其理化机制
  • 批准号:
    21247021
  • 财政年份:
    2009
  • 资助金额:
    $ 5.44万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Creation of Mechanobiology Based on Mechanosensitive Channels
基于力敏感通道的力生物学的创建
  • 批准号:
    16GS0308
  • 财政年份:
    2004
  • 资助金额:
    $ 5.44万
  • 项目类别:
    Grant-in-Aid for Creative Scientific Research
Analyses of activation mechanisms of cell mechanosensor at nano- and microlevels.
纳米和微米水平上细胞机械传感器的激活机制分析。
  • 批准号:
    15086207
  • 财政年份:
    2003
  • 资助金额:
    $ 5.44万
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas
STUDY ON THE STRUCTURE FUNCTION AND PHYSIOLOGICAL ROLES OF SA CHANNELS
SA通道的结构功能及生理作用研究
  • 批准号:
    13480216
  • 财政年份:
    2001
  • 资助金额:
    $ 5.44万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
CELL REMODELING BY MECHANICAL STIMULI : ROLE OF FOVAL ADHESION MOLECULES IN POLARITY FORMATION
机械刺激的细胞重塑:卵泡粘附分子在极性形成中的作用
  • 批准号:
    10480180
  • 财政年份:
    1998
  • 资助金额:
    $ 5.44万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
STUDY ON THE DEVELOPMENT OF MOLECULAR BIOLOGY AND PHYSIOLOGY OF SA CHANNELS
SA通道的分子生物学和生理学发展研究
  • 批准号:
    09044283
  • 财政年份:
    1997
  • 资助金额:
    $ 5.44万
  • 项目类别:
    Grant-in-Aid for international Scientific Research
Joint Study on the Molecular Biology of SA Channels
SA通道分子生物学联合研究
  • 批准号:
    07044245
  • 财政年份:
    1995
  • 资助金额:
    $ 5.44万
  • 项目类别:
    Grant-in-Aid for international Scientific Research

相似海外基金

Elucidation of abnormal calcium signal response in keloid-derived fibroblasts to stretch stimuli
阐明瘢痕疙瘩来源的成纤维细胞对拉伸刺激的异常钙信号反应
  • 批准号:
    19K10009
  • 财政年份:
    2019
  • 资助金额:
    $ 5.44万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The effect of stretch stimuli on human skin equivalents
拉伸刺激对人体皮肤等效物的影响
  • 批准号:
    26462732
  • 财政年份:
    2014
  • 资助金额:
    $ 5.44万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Postural responses to skin stretch stimuli around the hip, knee and ankle during quiet standing
安静站立时臀部、膝盖和脚踝周围皮肤拉伸刺激的姿势反应
  • 批准号:
    26560324
  • 财政年份:
    2014
  • 资助金额:
    $ 5.44万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Cloning and Analysis of the Gene Induced by Cyclic Stretch Stimuli
循环拉伸刺激诱导基因的克隆与分析
  • 批准号:
    11671418
  • 财政年份:
    1999
  • 资助金额:
    $ 5.44万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了