A novel telomerase expressing lung fibroblast phenotype

表达肺成纤维细胞表型的新型端粒酶

基本信息

  • 批准号:
    7247939
  • 负责人:
  • 金额:
    $ 35.33万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2004
  • 资助国家:
    美国
  • 起止时间:
    2004-07-05 至 2009-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Increased numbers of fibroblasts are a key feature of pulmonary fibrosis, and their coalescence in densely populated cell formations, termed fibroblastic foci, is a diagnostic histopathological feature of idiopathic pulmonary fibrosis (IPF). Increased proliferation is a likely mechanism for this increase in fibroblasts whose phenotype is distinct from cells isolated from normal lung. Interestingly a new fibroblast phenotype is found to emerge in animal models of lung injury and fibrosis characterized by the expression of telomerase activity. While telomerase activity is associated with increased proliferative capacity and life span in certain cells during early development and many tumor cells, its significance in the pathogenesis of pulmonary fibrosis is unknown. In this project it is hypothesized that emergence de novo of a telomerase-expressing fibroblast phenotype is induced by certain factors resulting in increased cell proliferation and/or survival. This would increase the pool size of proliferative cells serving as an intermediate differentiated population that can terminally differentiate to the myofibroblast phenotype. Four specific aims are proposed to test this hypothesis. First, the mechanism of telomerase induction will be studied in lung fibroblasts. The telomerase gene and its 5'-flanking sequences will be cloned for analysis of transcriptional regulation. Second, the relationship between the telomerase expressing and myofibroblast phenotypes will be examined by analyzing the relationship between telomerase and (-smooth muscle actin gene expression, and whether the transcriptional regulatory mechanisms for both genes are somehow related in a functionally meaningful way in terms of cellular differentiation. Third, the functional significance of telomerase expression will be analyzed by comparing telomere length with telomerase expression in vivo and in vitro, and whether telomerase expression endow cells with differential characteristics with respect to response to growth factors and/or apoptotic signals. Finally, the role of telomerase in pulmonary fibrosis will be examined in vivo in the bleomycin model by use of telomerase (either telomerase reverse transcriptase or telomerase RNA component) knockout mice as well as specific telomerase inhibitors. By using these combined approaches, new insights into the potential role and significance of this telomerase expressing phenotype will be uncovered, which may prove to be useful for devising future novel therapeutic approaches.
描述(由申请人提供):成纤维细胞数量的增加是肺纤维化的关键特征,它们在密集的细胞形成中聚集,称为成纤维细胞灶,是特发性肺纤维化(IPF)的诊断组织病理学特征。增殖增加可能是成纤维细胞增加的机制,其表型与从正常肺中分离的细胞不同。有趣的是,在以端粒酶活性表达为特征的肺损伤和纤维化动物模型中发现了一种新的成纤维细胞表型。虽然端粒酶活性与早期发育过程中某些细胞和许多肿瘤细胞的增殖能力和寿命增加有关,但其在肺纤维化发病机制中的意义尚不清楚。在这个项目中,假设表达成纤维细胞表型的端粒酶的出现是由某些因素诱导的,导致细胞增殖和/或存活增加。这将增加增殖细胞池的大小,作为中间分化群体,最终分化为肌成纤维细胞表型。为了验证这一假设,提出了四个具体目标。首先,研究端粒酶诱导肺成纤维细胞的机制。克隆端粒酶基因及其5′侧序列,分析其转录调控作用。其次,通过分析端粒酶与平滑肌肌动蛋白基因表达之间的关系,以及两种基因的转录调控机制是否在细胞分化方面以某种功能上有意义的方式相关,来研究端粒酶表达与肌成纤维细胞表型之间的关系。第三,端粒酶表达的功能意义将通过体内和体外端粒长度与端粒酶表达的比较,以及端粒酶表达是否赋予细胞在对生长因子和/或凋亡信号的反应方面的差异特征来分析。最后,端粒酶在肺纤维化中的作用将通过使用端粒酶(端粒酶逆转录酶或端粒酶RNA成分)敲除小鼠以及特定的端粒酶抑制剂在博来霉素模型中进行体内检测。通过使用这些联合方法,将发现对端粒酶表达表型的潜在作用和意义的新见解,这可能对设计未来的新治疗方法有用。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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

{{ 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 }}

SEM H PHAN其他文献

SEM H PHAN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('SEM H PHAN', 18)}}的其他基金

The role of Tet1 in myofibroblast differentiation
Tet1在肌成纤维细胞分化中的作用
  • 批准号:
    10371162
  • 财政年份:
    2021
  • 资助金额:
    $ 35.33万
  • 项目类别:
The role of Tet1 in myofibroblast differentiation
Tet1在肌成纤维细胞分化中的作用
  • 批准号:
    10201053
  • 财政年份:
    2021
  • 资助金额:
    $ 35.33万
  • 项目类别:
The role of Tet1 in myofibroblast differentiation
Tet1在肌成纤维细胞分化中的作用
  • 批准号:
    10586143
  • 财政年份:
    2021
  • 资助金额:
    $ 35.33万
  • 项目类别:
BM alterations in exacerbation of pulmonary fibrosis
肺纤维化恶化中的 BM 改变
  • 批准号:
    9898440
  • 财政年份:
    2018
  • 资助金额:
    $ 35.33万
  • 项目类别:
Resistin-like molecules in pulmonary fibrosis
肺纤维化中的抵抗素样分子
  • 批准号:
    8666587
  • 财政年份:
    2013
  • 资助金额:
    $ 35.33万
  • 项目类别:
Resistin-like molecules in pulmonary fibrosis
肺纤维化中的抵抗素样分子
  • 批准号:
    8420737
  • 财政年份:
    2013
  • 资助金额:
    $ 35.33万
  • 项目类别:
The role of C/EBP in pulmonary fibrosis
C/EBP在肺纤维化中的作用
  • 批准号:
    8242757
  • 财政年份:
    2011
  • 资助金额:
    $ 35.33万
  • 项目类别:
The role of C/EBP in pulmonary fibrosis
C/EBP在肺纤维化中的作用
  • 批准号:
    7680429
  • 财政年份:
    2009
  • 资助金额:
    $ 35.33万
  • 项目类别:
FIZZ1 Expression and Function in Pulmonary Fibrosis
FIZZ1 在肺纤维化中的表达和功能
  • 批准号:
    7350227
  • 财政年份:
    2007
  • 资助金额:
    $ 35.33万
  • 项目类别:
FIZZ1 Expression and Function in Pulmonary Fibrosis
FIZZ1 在肺纤维化中的表达和功能
  • 批准号:
    7312445
  • 财政年份:
    2006
  • 资助金额:
    $ 35.33万
  • 项目类别:

相似海外基金

Influence of the polymorphism of 5'-flanking region of SAA1 gene on SAA1 transcriptional activity
SAA1基因5侧翼区多态性对SAA1转录活性的影响
  • 批准号:
    13670479
  • 财政年份:
    2001
  • 资助金额:
    $ 35.33万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Characterization of The 5'-Flanking Region of the Stress Response Gene, Osp94
应激反应基因 Osp94 5-侧翼区域的表征
  • 批准号:
    12672132
  • 财政年份:
    2000
  • 资助金额:
    $ 35.33万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Mdecular cloning and analysis of S' -flanking region of human MYPT1 gene
人MYPT1基因S侧翼区的分子克隆与分析
  • 批准号:
    10670645
  • 财政年份:
    1998
  • 资助金额:
    $ 35.33万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
ANALYSIS OF CYCLIN D1 GENE EXPRESSION BY METHYLATION OF CpG ISLAND LOCATED 5'-FLANKING REGION
5-侧翼区 CpG 岛甲基化分析细胞周期蛋白 D1 基因表达
  • 批准号:
    09670226
  • 财政年份:
    1997
  • 资助金额:
    $ 35.33万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
ANALYSIS OF TWO PROMOTERS AND 5'FLANKING REGION OF RAT SERINE : PYRUVATE AMINOTRANSFERASE GENE
大鼠丝氨酸丙酮酸转氨酶基因的两个启动子和5侧翼区的分析
  • 批准号:
    05680546
  • 财政年份:
    1993
  • 资助金额:
    $ 35.33万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Characterization of 5 prime flanking region of 230 kDa bullous pemphigoid antigen gene
230 kDa 大疱性类天疱疮抗原基因 5 主要侧翼区域的表征
  • 批准号:
    05670718
  • 财政年份:
    1993
  • 资助金额:
    $ 35.33万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Syndrome of extreme insulin resistance due to decreased promoter activity of 5'-flanking region of insulin receptor gene.
由于胰岛素受体基因 5-侧翼区域启动子活性降低而导致的极端胰岛素抵抗综合征。
  • 批准号:
    03454513
  • 财政年份:
    1991
  • 资助金额:
    $ 35.33万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了