NEUREGULINS AND THEIR RECEPTORS IN LUNG DEVELOPMENT

肺发育中的神经调节蛋白及其受体

• 批准号: 6931956
• 负责人: CHRISTIANE E DAMMANN
• 金额: $ 12.83万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6931956
• 关键词: SDS polyacrylamide gel electrophoresis; animal tissue; biological signal transduction; cell cell interaction; cell growth regulation; cell proliferation; embryo /fetus tissue /cell culture; enzyme linked immunosorbent assay; fibroblasts; growth factor receptors; immunocytochemistry; immunoprecipitation; laboratory mouse; lipid biosynthesis; lung development; mesenchyme; organ culture; polymerase chain reaction; pulmonary surfactants; respiratory epithelium; scintillation counter; thin layer chromatography; western blottings

Christiane E.L. Dammann, M.D. is currently a research and clinical fellow in the Division of Newborn Medicine at New England Medical Center and a research fellow in the Division of Signal Transduction at the Beth Israel Hospital. She is applying for this award to develop a career as an independent scientist in Neonatology with her research focused on fetal lung development. She will accomplish this goal with the help of her two mentors Dr. Nielsen and Dr. Cantley. Pulmonary surfactant consists of phospholipids and apoproteins and is critical for lung maturation. Surfactant deficiency during fetal lung development contributes to neonatal distress syndrome. Fibroblast- Pneumocyte-Factor (FPF) is a fibroblast derived polypeptide differentiation factor that regulates surfactant synthesis in lung type II epithelial cells. We have strong evidence that Neuregulin-1 (NRG1), a stromal-derived growth factor previously implicated in mammary gland epithelial cell maturation, is a critical component of FPF. For our preliminary studies we have used MLE 12 cells, which display characteristics of fetal type II cells. We now propose to investigate further the role of NRGs and their receptors in regulating surfactant synthesis during lung development using primary fetal mouse cells. The specific aims of this proposal are threefold. First, the role of the NRGs in the regulation of fibroblast-type II cell communication leading to surfactant synthesis will be determined. Second the regulation of NRG expression / production during lung development will be investigated. Third, the question which of the erbB receptors and intracellular ligands are involved in the NRG signaling pathway in mesenchymal-type II cell communication will be studied. The goal is to gain further insight into the regulation of surfactant synthesis. This should contribute to the development of diagnostic and therapeutic strategies that reduce the burden of acute and chronic lung disease among preterm infants.

克里斯蒂安·E.L. Dammann 医学博士目前是新英格兰医学中心新生儿医学科的研究员和临床研究员，也是贝斯以色列医院信号转导科的研究员。她正在申请该奖项，以发展作为新生儿学独立科学家的职业生涯，她的研究重点是胎儿肺部发育。她将在两位导师尼尔森博士和坎特利博士的帮助下实现这一目标。肺表面活性物质由磷脂和脱辅基蛋白组成，对于肺成熟至关重要。胎儿肺部发育过程中表面活性剂的缺乏会导致新生儿窘迫综合征。成纤维细胞肺细胞因子 (FPF) 是一种成纤维细胞衍生的多肽分化因子，可调节 II 型肺上皮细胞中表面活性剂的合成。我们有强有力的证据表明 Neuregulin-1 (NRG1) 是一种基质源性生长因子，之前与乳腺上皮细胞成熟有关，是 FPF 的关键成分。在我们的初步研究中，我们使用了 MLE 12 细胞，它显示出胎儿 II 型细胞的特征。我们现在建议使用原代胎儿小鼠细胞进一步研究 NRG 及其受体在肺发育过程中调节表面活性剂合成的作用。该提案有三个具体目标。首先，将确定 NRG 在调节 II 型成纤维细胞通讯导致表面活性剂合成中的作用。其次，将研究肺发育过程中 NRG 表达/产生的调节。第三，将研究erbB受体和细胞内配体中的哪一个参与间充质II型细胞通讯中的NRG信号通路。目标是进一步了解表面活性剂合成的调节。这应该有助于制定减少早产儿急性和慢性肺部疾病负担的诊断和治疗策略。

项目成果

Neuregulin-1, the fetal endothelium, and brain damage in preterm newborns.

• DOI: 10.1016/j.bbi.2009.08.012
• 发表时间: 2010-07
• 期刊: BRAIN BEHAVIOR AND IMMUNITY
• 影响因子: 15.1
• 作者: Hoffmann, Insa;Bueter, Wolfgang;Zscheppang, Katja;Brinkhaus, Maria-Jantje;Liese, Andrea;Riemke, Stefan;Doerk, Thilo;Dammann, Olaf;Dammann, Christiane E. L.
• 通讯作者: Dammann, Christiane E. L.

Neuregulin receptor ErbB4 functions as a transcriptional cofactor for the expression of surfactant protein B in the fetal lung.

神经调节蛋白受体 ErbB4 作为胎儿肺中表面活性蛋白 B 表达的转录辅助因子。

• DOI: 10.1165/rcmb.2010-0179oc
• 发表时间: 2011
• 期刊: American journal of respiratory cell and molecular biology
• 影响因子: 6.4
• 作者: Zscheppang,Katja;Dörk,Thilo;Schmiedl,Andreas;Jones,FrankE;Dammann,ChristianeEL
• 通讯作者: Dammann,ChristianeEL

Estrogen-induced upregulation of Sftpb requires transcriptional control of neuregulin receptor ErbB4 in mouse lung type II epithelial cells.

雌激素诱导的 Sftpb 上调需要小鼠 II 型肺上皮细胞中神经调节蛋白受体 ErbB4 的转录控制。

• DOI: 10.1016/j.bbamcr.2011.06.020
• 发表时间: 2011
• 期刊: Biochimica et biophysica acta
• 作者: Zscheppang,Katja;Konrad,Mirja;Zischka,Melanie;Huhn,Verena;Dammann,ChristianeEL
• 通讯作者: Dammann,ChristianeEL