• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Studies on the growth of smooth muscle from the airways of hyperresponsive rats.
【24h】

Studies on the growth of smooth muscle from the airways of hyperresponsive rats.

机译：高反应性大鼠气道平滑肌生长的研究。

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

The aim of this work was to study proliferative growth of airway smooth muscle (ASM) cells from Fisher rats, a highly inbred strain known to have an increased amount of ASM in vivo, and airway hyperresponsiveness, when compared to control Lewis rats. Airway hyperresponsiveness is a hallmark of asthma, and ASM provides the contractile force which narrows or closes the airways during asthmatic episodes. Growth of ASM in asthma and animal models of asthma is well documented, and is likely to be a crucial determinant of an excessive airway response to contractile agonists. However, the mechanisms of ASM growth in asthma are unknown. Because ASM cells proliferate when exposed to inflammatory mediators, ASM growth in asthma has been assumed to be a sequel of inflammation of the airways. This thesis now presents data supporting an alternative hypothesis for the evolution of increased smooth muscle mass in asthma. Studies on highly inbred rats suggest that enhanced responsiveness of ASM cells to mitogens is a genetically determined phenotype, and may thus predispose to an increased mass and contractility of ASM in vivo. Thus, an inborn susceptibility for enhanced ASM growth may lead to airway hyperresponsiveness. The proliferative response to mitogenic stimulation in ASM cells from hyperresponsive Fisher rats was enhanced when compared to the response of ASM cells from control Lewis rats. This enhancement was inherent to ASM cells, persisting over multiple passages in culture, and the mechanisms responsible were operative in G0 or G1 of the cell cycle. An enhanced proliferative response of Fisher ASM cells was selectively induced by a subset of the growth factors examined. These included fetal bovine serum (FBS), epidermal growth factor (EGF), and the AA or AB isoforms of platelet-derived growth factor (PDGF). The growth response of Fisher ASM cells to other mitogens tested was not enhanced with respect to Lewis ASM cells, indicating that the mechanisms responsible for enhanced Fisher ASM cell growth are not at a point in growth signalling pathways which is converged upon by all mitogens. The data suggest that several mechanisms can be ruled out as potential explanations of enhanced Fisher ASM cell growth. These include differences in basal levels of mitogen activated protein (MAP) kinases or PDGF receptors, as well as differences in phospholipase C (PLC)-mediated growth signals, intracellular calcium responses, and tyrosine phosphorylation of MAP kinases, PDGF receptors, or a number of other cellular proteins. Instead it appears that enhanced Fisher ASM cell growth is mediated by phorbol ester-sensitive isoforms, of the serine/threonine specific protein kinase C (PKC), and is associated with enhanced serine/threonine phosphorylation of a 115 kD protein. These findings lay the groundwork for characterizing a model of genetic predisposition to enhanced ASM growth. This model may prove a valuable tool for elucidating the mechanisms of ASM growth, and may thus contribute to the development of new strategies for the treatment of asthma.
机译：这项工作的目的是研究费舍尔大鼠的气道平滑肌（ASM）细胞的增殖性生长，这是一种高度近交的品系，与之相比，该品系的体内ASM含量增加，并且气道高反应性来控制刘易斯老鼠。气道高反应性是哮喘的标志，而ASM提供的收缩力可在哮喘发作期间缩小或关闭气道。哮喘和哮喘动物模型中ASM的生长已得到充分证明，并且可能是对收缩性激动剂过度气道反应的关键决定因素。但是，哮喘中ASM生长的机制尚不清楚。由于ASM细胞在暴露于炎症介质时会增殖，因此哮喘中ASM的生长被认为是气道炎症的后遗症。现在，本论文提出的数据支持了哮喘平滑肌质量增加演变的另一种假设。对高度近交系大鼠的研究表明，ASM细胞对有丝分裂原的反应性增强是一种遗传决定的表型，因此可能会导致ASM体内质量和收缩性增加。因此，天生对增强ASM增长的敏感性可能导致气道高反应性。与来自对照Lewis大鼠的ASM细胞的反应相比，增强了高反应性Fisher大鼠的ASM细胞对有丝分裂刺激的增殖反应。这种增强是ASM细胞固有的，可以在培养中多次传代，并且在细胞周期的G 0 或G 1 中起作用。被检查的一部分生长因子选择性诱导了Fisher ASM细胞增强的增殖反应。这些包括胎牛血清（FBS），表皮生长因子（EGF）以及血小板衍生生长因子（PDGF）的AA或AB亚型。相对于Lewis ASM细胞，Fisher ASM细胞对其他受试有丝分裂原的生长反应并未增强，这表明负责Fisher Fisher ASM细胞生长增强的机制并不在所有有丝分裂原都收敛的生长信号通路中。数据表明，可以排除几种机制作为增强的Fisher ASM细胞生长的潜在解释。这些包括有丝分裂原活化蛋白（MAP）激酶或PDGF受体的基础水平的差异，以及磷脂酶C（PLC）介导的生长信号，细胞内钙反应以及MAP激酶，PDGF受体或许多酪氨酸磷酸化的差异其他细胞蛋白。相反，似乎费舍尔ASM细胞的生长增强是由丝氨酸/苏氨酸特异性蛋白激酶C（PKC）的佛波酯敏感同工型介导的，并且与115 kD蛋白的丝氨酸/苏氨酸磷酸化作用增强有关。这些发现为表征增强ASM生长的遗传易感性模型奠定了基础。该模型可能证明是阐明ASM增长机制的有价值的工具，因此可能有助于开发治疗哮喘的新策略。

著录项

  • 作者

    Zacour, Mary Eleanor.;

  • 作者单位

    McGill University (Canada).;

  • 授予单位 McGill University (Canada).;
  • 学科 Biology Cell.; Biology Molecular.
  • 学位 Ph.D.
  • 年度 1998
  • 页码 185 p.
  • 总页数 185
  • 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

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