THE ROLE OF INSULIN IN HUMAN FETAL LUNG DEVELOPMENT
胰岛素在人类胎儿肺发育中的作用
基本信息
- 批准号:6628968
- 负责人:
- 金额:$ 22.05万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1995
- 资助国家:美国
- 起止时间:1995-09-01 至 2005-01-31
- 项目状态:已结题
- 来源:
- 关键词:biological signal transduction cell line clinical research developmental genetics diabetes mellitus embryo /fetus protein gene expression genetic regulatory element histogenesis hormone regulation /control mechanism human fetus tissue immunocytochemistry insulin insulin receptor lung lung development phosphatidylinositol 3 kinase phosphorylation protein kinase protein localization protein protein interaction proteolipids pulmonary surfactants respiratory distress syndrome of newborn respiratory epithelium transcription factor
项目摘要
DESCRIPTION: (Adapted from the Investigator's Abstract): The hypothesis is that
delayed lung development in the fetus of the diabetic woman is related to
surfactant-associated protein deficiency caused by high levels of insulin. Aim
1 is to elucidate the signal transduction pathways involved in insulin-mediated
inhibition of SP-A and SP-B gene expression. Signal transduction inhibitors,
enzyme assays, characterization of signaling intermediates and transfection
with dominant negative and constitutively active constructs will be used to
test the hypothesis that the PI-3K signal transduction pathway mediates the
effects of insulin. Aim 2 is to identify the cis-acting elements in the SP-A
and SP-B genes which mediate the inhibitory effects of insulin. Luciferase
reporter gene constructs will be used to localize inhibitory insulin response
elements in the 5' flanking region of the human SP-A1 and SP-A2 genes. Aim 3 is
to identify the transcription factors that interact with the SP-A1 and SP-B
insulin response elements. Electrophoretic mobility shift assays will be used
to test the hypothesis that HNF-3a and C/EBPa mediate the insulin-induced
inhibition of SP-A and SP-B gene expression. Aim 4 is to describe the molecular
events (phosphorylation, localization, and/or changes in gene expression) that
link signal transduction to transcription factors which interact with the
insulin response elements in the SP-A1 and SP-B genes.
描述:(改编自研究者摘要):假设是,
糖尿病妇女胎儿肺发育延迟与
由高水平胰岛素引起的表面活性剂相关蛋白缺乏症。目的
1是阐明参与胰岛素介导的细胞凋亡的信号转导途径,
抑制SP-A和SP-B基因表达。信号转导抑制剂,
酶测定、信号传导中间体的表征和转染
具有显性阴性和组成型活性的构建体将用于
检验PI-3 K信号转导通路介导
胰岛素的作用。目的二是鉴定SP-A中的顺式作用元件
和SP-B基因介导胰岛素的抑制作用。素酶
报告基因构建体将用于定位抑制性胰岛素应答
人SP-A1和SP-A2基因5 ′侧翼区的元件。目标3是
鉴定与SP-A1和SP-B相互作用的转录因子
胰岛素反应元件。将使用电泳迁移率变动试验
为了验证HNF-3a和C/EBPa介导胰岛素诱导的胰岛素依赖性高血压的假说,
抑制SP-A和SP-B基因表达。目的4是描述分子
事件(磷酸化,定位和/或基因表达的变化),
将信号转导与转录因子联系起来,
SP-A1和SP-B基因中的胰岛素反应元件。
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)
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Jeanne Marie Snyder其他文献
Jeanne Marie Snyder的其他文献
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{{ truncateString('Jeanne Marie Snyder', 18)}}的其他基金
THE ROLE OF INSULIN IN HUMAN FETAL LUNG DEVELOPMENT
胰岛素在人类胎儿肺发育中的作用
- 批准号:
6702582 - 财政年份:1995
- 资助金额:
$ 22.05万 - 项目类别:
THE ROLE OF INSULIN IN HUMAN FETAL LUNG DEVELOPMENT
胰岛素在人类胎儿肺发育中的作用
- 批准号:
6285913 - 财政年份:1995
- 资助金额:
$ 22.05万 - 项目类别:
THE ROLE OF INSULIN IN HUMAN FETAL LUNG DEVELOPMENT
胰岛素在人类胎儿肺发育中的作用
- 批准号:
6498906 - 财政年份:1995
- 资助金额:
$ 22.05万 - 项目类别:
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