• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Insulin-like growth factor-I in fibroproliferative acute respiratory distress syndrome: The molecular mechanisms of tumor necrosis factor regulated insulin-like growth factor-I production in macrophages.
【24h】

Insulin-like growth factor-I in fibroproliferative acute respiratory distress syndrome: The molecular mechanisms of tumor necrosis factor regulated insulin-like growth factor-I production in macrophages.

机译：纤维增生性急性呼吸窘迫综合征中的胰岛素样生长因子-I：肿瘤坏死因子调节巨噬细胞中胰岛素样生长因子-I产生的分子机制。

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

Insulin-like Growth Factor-I (IGF-I) is a soluble polypeptide growth factor that we have found elevated in the lungs of individuals with fibroproliferative acute respiratory distress syndrome (FP-ARDS). IGF-I contributes to the fibroproliferative process in the lungs of individuals with FP-ARDS evidenced by positive correlations between enhanced IGF-I protein and each of collagen III and Proliferating Cell Nuclear Antigen, a marker of dividing cells, in alveolar epithelial lining fluids and lung biopsy specimens. Macrophages in the lungs of individuals with FP-ARDS contain IGF-I protein by immunohistochemical analysis and IGF-I mRNA detected by reverse transcription polymerase chain reaction, suggesting macrophages are a source of IGF-I in the lung. We sought to determine the molecular mechanism of IGF-I production in macrophages. Tumor Necrosis Factor, a pro-inflammatory cytokine that is also elevated in the lungs of individuals with FP-ARDS, stimulated an increased level of IGF-I mRNA in murine bone marrow derived macrophages in vitro, suggesting TNF may stimulate increased IGF-I production. We show that mitogen activated protein kinase intracellular signal transduction pathways including Erk, JNK and p38 participate in TNF induced IGF-I mRNA production in murine bone marrow derived macrophages. Further, use of a 1711 base pair rat I4GF-I promoter:luciferase reporter construct showed that the IGF-I promoter is transcriptionally active in murine macrophage cell lines, though this regulatory region showed no TNF-stimulated activity. Therefore, we cloned and sequenced a putative 1829 base pair regulatory region upstream of the murine IGF-I exon 1 translational start site. This murine IGF-I region contains potential transcriptional regulatory elements, though we were unable to show functional activity in transfected systems. These studies provide a better understanding of the regulation of IGF-I production in macrophages and a potential role of IGF-I production in the lungs of individuals with FP-ARDS.
机译：胰岛素样生长因子-I（IGF-1）是一种可溶性多肽生长因子，我们发现它在患有纤维增生性急性呼吸窘迫综合征（FP-ARDS）的人的肺中升高。 IGF-I有助于FP-ARDS个体肺部的纤维增生过程，其表现为增强的IGF-I蛋白与每种胶原蛋白III和肺泡上皮衬里液中的分裂细胞标志物增殖细胞核抗原之间的正相关性。肺活检标本。 FP-ARDS个体肺中的巨噬细胞通过免疫组织化学分析含有IGF-I蛋白，并通过逆转录聚合酶链反应检测到IGF-I mRNA，这表明巨噬细胞是肺中IGF-I的来源。我们试图确定巨噬细胞中IGF-1产生的分子机制。肿瘤坏死因子是一种促炎细胞因子，在患有FP-ARDS的个体的肺中也升高，在体外刺激了小鼠骨髓衍生的巨噬细胞中IGF-I mRNA的水平升高，表明TNF可能刺激了IGF-I产生的增加。我们表明，包括Erk，JNK和p38在内的促分裂原活化蛋白激酶细胞内信号转导途径参与了TNF诱导的IGF-I mRNA在鼠骨髓衍生的巨噬细胞中的产生。此外，使用1711个碱基对的大鼠I4GF-1启动子：荧光素酶报道基因构建物表明，IGF-1启动子在鼠巨噬细胞系中具有转录活性，尽管该调节区没有显示出TNF刺激的活性。因此，我们克隆并测序了鼠IGF-1外显子1翻译起始位点上游的推测的1829个碱基对调控区。尽管我们无法在转染系统中显示功能活性，但该鼠类IGF-I区含有潜在的转录调控元件。这些研究提供了对巨噬细胞中IGF-I产生的调节的更好理解，以及对FP-ARDS患者的肺中IGF-I产生的潜在作用。

著录项

  • 作者

    Krein, Peter M.;

  • 作者单位

    University of Calgary (Canada).;

  • 授予单位 University of Calgary (Canada).;
  • 学科 Biology Cell.;Health Sciences Immunology.;Health Sciences Pathology.
  • 学位 Ph.D.
  • 年度 2003
  • 页码 251 p.
  • 总页数 251
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 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