• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Regulation of retinal endothelial cells and pericytes by VEGF, TGF-beta1 and SPARC.
【24h】

Regulation of retinal endothelial cells and pericytes by VEGF, TGF-beta1 and SPARC.

机译：VEGF，TGF-beta1和SPARC对视网膜内皮细胞和周细胞的调节。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Ocular diseases characterized by retinal neovascularization are among the principal causes of visual loss worldwide. In an effort to understand the components of the retinal angiogenesis and its regulation by various molecules, I developed a procedure to isolate retinal microvascular endothelial cells (EC) and pericytes from the primate and bovine species. This was important because retinal capillary EC are different from EC derived from other vascular beds. Retinal EC expressed von Willebrand factor, acetylated low-density lipoprotein, CD31, and did not contain smooth muscle a-actin. Monkey retinal EC could be maintained to passage 3, whereas bovine retinal EC could be maintained to passage 8. Subconfluent cultures of monkey retinal EC secreted extracellular matrix proteins that included fibronectin, laminin, collagen types I and IV, and SPARC. VEGF and bFGF both stimulated retinal EC replication, which was also elevated under hypoxia. The synergism of VEGF and bFGF on retinal EC proliferation and cell invasion was observed in a 3-dimensional assay but not in 2-dimensional dish culture.;Unlike VEGF and bFGF, the role of transforming growth factor (TGF)-;SPARC is expressed in a variety of tissues during embryogenesis and remodeling, and is believed to regulate vascular morphogenesis and cellular differentiation. Although usually limited in normal adult tissues, SPARC is expressed at significant levels in the adult bovine retina, whereas newborn calf retina showed a similar expression pattern with a greatly reduced level. Strong reactivity with anti-SPARC antibody was found in the soma of ganglion cells and their axons. SPARC was also present in retinal astrocytes but not in Mueller cells, capillaries of the inner retina but not large vessels. To determine the significance of SPARC expression in retina, I test two hypotheses. (1) SPARC has counteradhesive properties that can cause cell rounding, and would thus induce retinal EC apoptosis in vitro; (2) SPARC is one of the endogenous inhibitors that either maintain the quiescence of retinal EC under normal physiological conditions or inhibit retinal neovascularization. My conclusions are that SPARC or its peptides did not induce retinal EC apoptosis in vitro under the experimental conditions used; SPARC and its peptides were potent inhibitors of retinal EC replication, as they effectively inhibited EC proliferation induced by retinal extract. Future study will focus on testing the role of SPARC in retinal neovascularization through the use of wild-type vs. SPARC-null mice in an animal model of the retinopathy, and on delineating mechanisms whereby SPARC regulates retinal pericyte function.
机译：以视网膜新血管形成为特征的眼疾病是全世界视力丧失的主要原因之一。为了了解视网膜血管生成的组成及其受各种分子的调节，我开发了一种从灵长类和牛类动物中分离视网膜微血管内皮细胞（EC）和周细胞的程序。这很重要，因为视网膜毛细血管EC与源自其他血管床的EC不同。视网膜EC表达von Willebrand因子，乙酰化的低密度脂蛋白CD31，并且不含平滑肌α-肌动蛋白。猴子视网膜EC可以维持到第3代，而牛视网膜EC可以维持到第8代。猴视网膜EC的亚汇合培养物分泌细胞外基质蛋白，包括纤连蛋白，层粘连蛋白，I型和IV型胶原以及SPARC。 VEGF和bFGF均可刺激视网膜EC复制，在缺氧条件下也可升高。在3维分析中观察到VEGF和bFGF对视网膜EC增殖和细胞侵袭的协同作用，但在二维培养皿中未观察到。;与VEGF和bFGF不同，表达了转化生长因子（TGF）-; SPARC的作用在胚胎发生和重塑期间各种组织中的表达，并且据信调节血管形态发生和细胞分化。尽管通常在正常的成人组织中受到限制，但SPARC在成人的牛视网膜中的表达水平很高，而新生的小牛视网膜则显示出相似的表达模式，但表达水平大大降低。在神经节细胞及其轴突的体中发现了与抗SPARC抗体的强反应性。 SPARC也存在于视网膜星形胶质细胞中，但不存在于Mueller细胞，视网膜内的毛细血管中，但不存在于大血管中。为了确定SPARC在视网膜中表达的重要性，我测试了两个假设。 （1）SPARC具有抗黏附特性，可引起细胞变圆，从而在体外诱导视网膜EC凋亡； （2）SPARC是在正常生理条件下维持视网膜EC静止或抑制视网膜新血管形成的内源性抑制剂之一。我的结论是，在所使用的实验条件下，SPARC或其肽在体外不会诱导视网膜EC凋亡。 SPARC及其肽是视网膜EC复制的有效抑制剂，因为它们有效抑制了视网膜提取物诱导的EC增殖。未来的研究将侧重于通过在视网膜病动物模型中使用野生型与SPARC空小鼠来测试SPARC在视网膜新血管形成中的作用，以及描述SPARC调节视网膜周细胞功能的机制。

著录项

  • 作者

    Yan, Qi.;

  • 作者单位

    University of Washington.;

  • 授予单位 University of Washington.;
  • 学科 Biology Molecular.;Biology Cell.;Health Sciences Ophthalmology.
  • 学位 Ph.D.
  • 年度 1998
  • 页码 113 p.
  • 总页数 113
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子遗传学;细胞生物学;
  • 关键词

  • 入库时间 2022-08-17 11:48:41

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号