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首页> 外文学位 >Laminin-5 mediates vascular smooth muscle cell response to growth factors.
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Laminin-5 mediates vascular smooth muscle cell response to growth factors.

机译：层粘连蛋白5介导血管平滑肌细胞对生长因子的反应。

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摘要

The development and normal function of cells in the body depend upon interactions with other molecules. One such group of molecules, referred to as the extracellular matrix (ECM), is secreted by subsets of epithelial, endothelial, and mesenchymal cells within multicellular organisms. The laminin families comprise a set of soluble ECM glycoproteins that are required for structural integrity and development in many epithelial tissues. Ln-5 is a laminin isoform composed of three subunits: α3, β3, and γ2. In this study, I sought to determine temporal and spatial patterns of ln-5 expression in non epithelial tissues. Using an enzyme-linked immunofluorescence amplification system and newly developed photobleaching treatment, I observed ln-5 expression in previously undocumented sites including vascular smooth muscle cells (VSMC) of the aorta, pulmonary arteries, and also in bone and cartilage. In adult animals, VSMC are terminally differentiated and control blood flow and contraction in response to various chemical and mechanical stimuli. However, during the formation of atherosclerotic and restenotic lesions, VSMCs revert to a synthetic a phenotype characterized by a secretory-, proliferative-, and migratory-active state. I analyzed the functional significance of ln-5 expression, which is upregulated by growth factors induced following arterial injury. I found that ln-5 significantly altered the proliferation of VSMC in response to platelet-derived growth factor (PDGF-BB), a potent mitogen and chemoattractant for VSMC. I demonstrated that the α6β1 and the α6β4 integrin complex may be responsible for the initial VSMC adhesion to ln-5. I also demonstrated that ln-5 does not support haptotactic VSMC migration, however PDGF-BB-stimulation greatly enhanced VSMC migration on ln-5. I therefore postulated that PDGF-BB-stimulated MAPK activation is responsible for the increased migratory phenotype of VSMC on ln-5 and found stimulation of VSMC with PDGF-BB reduced VSMC adhesion to ln-5 and concomitantly increased VSMC migration on ln-5 while revealing detectable increases in ERK1/2 activation. As ln-5 is involved in the enhanced migration of various cell types, the increased production and decreased adhesion of VSMC on ln-5 may provide a mechanism for the design of novel and interesting targets in the prevention of pathological processes associated with the arterial vasculature, such as restenosis following angioplasty.
机译：人体细胞的发育和正常功能取决于与其他分子的相互作用。这样的一组分子，称为细胞外基质（ECM），由多细胞生物体内的上皮，内皮和间充质细胞的子集分泌。层粘连蛋白家族包含一组可溶性ECM糖蛋白，这是许多上皮组织中结构完整性和发育所必需的。 Ln-5是层粘连蛋白同种型，由三个亚基组成：α3，β3和γ2。在这项研究中，我试图确定非上皮组织中ln-5表达的时空格局。使用酶联免疫荧光扩增系统和新开发的光漂白疗法，我观察到ln-5在以前未记录的部位表达，包括主动脉的血管平滑肌细胞（VSMC），肺动脉以及骨骼和软骨。在成年动物中，VSMC最终分化并响应各种化学和机械刺激来控制血流和收缩。但是，在动脉粥样硬化和再狭窄病变的形成过程中，VSMC恢复为合成的表型，其特征在于分泌，增殖和迁移活跃状态。我分析了ln-5表达的功能意义，该意义被动脉损伤后诱导的生长因子上调。我发现ln-5可以响应血小板衍生的生长因子（PDGF-BB）来显着改变VSMC的增殖，PDGF-BB是VSMC的有力促细胞分裂剂和趋化因子。我证明了α6β1和α6β4整合素复合物可能是VSMC最初粘附到ln-5的原因。我还证明了ln-5不支持触觉式VSMC迁移，但是PDGF-BB刺激极大地增强了ln-5上的VSMC迁移。因此，我推测PDGF-BB刺激的MAPK活化是ln-5上VSMC迁移表型增加的原因，并发现PDGF-BB刺激VSMC降低了VSMC对ln-5的粘附，并同时增加了ln-5上VSMC的迁移揭示ERK1 / 2激活可检测到的增加。由于ln-5参与了各种细胞类型的迁移增强，VSMC在ln-5上的产量增加和粘附性降低可能为设计新颖有趣的靶标提供了机制，以预防与动脉血管相关的病理过程如血管成形术后的再狭窄。

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  • 作者

    Kingsley, Karl.;

  • 作者单位

    University of Nevada, Las Vegas.;

  • 授予单位 University of Nevada, Las Vegas.;
  • 学科 Biology Cell.; Biology Molecular.
  • 学位 Ph.D.
  • 年度 2001
  • 页码 199 p.
  • 总页数 199
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;分子遗传学;
  • 关键词

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