ErbB Signaling in Fetal Type II Cell Growth

胎儿 II 型细胞生长中的 ErbB 信号转导

• 批准号: 8197379
• 负责人: CHRISTIANE E DAMMANN
• 金额: $ 39.85万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-10 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8197379
• 关键词: 1-Phosphatidylinositol 3-Kinase; Address; Birth; Blocking Antibodies; Borderline Personality Disorder; Bronchopulmonary Dysplasia; Cell Differentiation process; Cell Nucleus; Cell Proliferation; Cells; Co-Immunoprecipitations; Confocal Microscopy; Development; Developmental Cell Biology; Developmental Process; Disease; Down-Regulation; Elements; Epidermal Growth Factor; Epidermal Growth Factor Receptor; Epithelial Cells; ErbB Receptor Family Protein; ErbB4 gene; Event; Fetal Lung; Goals; Growth; Growth and Development function; Indium; Ligands; Lung; Lung diseases; MAP Kinase Activation Pathway; MAP Kinase Gene; MAP Kinase Signaling Pathways; Mediating; Messenger RNA; Molecular Chaperones; Morbidity - disease rate; Mus; Neuregulins; Nuclear; Nuclear Receptors; Pathway interactions; Phosphorylation; Pregnancy; Premature Birth; Process; Production; Pulmonary Surfactant-Associated Protein B; Receptor Activation; Receptor Signaling; Relative (related person); Respiratory physiology; Role; Signal Transduction; Small Interfering RNA; System; Testing; Transgenic Organisms; Type II Epithelial Receptor Cell; Up-Regulation; cell growth; crosslink; cyclin D2; dimer; fetal; inhibitor/antagonist; insight; lung development; member; monomer; mortality; mutant; novel; novel therapeutics; receptor; research study; respiratory distress syndrome; response; surfactant; trafficking

PROPOSAL ABSTRACT Late gestation fetal lung development requires coordinated controls of type II cell proliferation and differentiation. While much progress has been made in determining the mechanisms controlling fetal type II cell differentiation, relatively little is known about the control of fetal type II cell proliferation and the mechanisms which coordinate these two important developmental processes. This proposal is focused on ErbB receptor signaling mechanisms as controlling elements in fetal type II cell proliferation. The ErbB receptor family is comprised of four members: the Epidermal Growth Factor Receptor (EGF-R), ErbB2, ErbB3, and ErbB4. Through a system of different ligands and different receptor dimer formation these receptors orchestrate diverse signaling responses to act as important regulators of cell proliferation and differentiation, especially during development. We have shown the importance of this system in type II cell differentiation. A paradigm of developmental cell biology is that cell proliferation and differentiation are in mechanistic tension, such that up regulation of one process is associated with down regulation of the other process. In this proposal our hypothesis is that ErbB receptor activation mediates fetal lung type II cell growth and differentiation, through diversification of receptor responses. We will address three Specific Aims: #1: Mechanisms controlling type II cell growth versus differentiation are controlled by differential ErbB receptor activity; #2: The mechanisms controlling fetal type II cell growth and differentiation utilize ErbB receptor dimers specific to each process; and #3: Determine the role of ErbB receptor nuclear localization in regulating fetal type II cell growth and differentiation. New insight into the mechanisms controlling fetal type II cell growth will contribute to our ability to develop new therapeutic strategies that will promote normal lung development following preterm birth or other developmental lung diseases.

建议书摘要 妊娠晚期胎肺发育需要II型细胞的协调控制 增殖分化。虽然在以下方面取得了很大进展 确定控制胎儿II型细胞分化的机制，相对 对于胎儿II型细胞增殖的控制和细胞因子的调控知之甚少 协调这两个重要发展过程的机制。 这一建议的重点是ErbB受体信号机制作为控制 胎儿II型细胞增殖的要素。ErbB受体家族包括 四个成员：表皮生长因子受体(EGF-R)，ErbB2，ErbB3， 和ErbB4。通过不同配体和不同受体二聚体的系统 形成这些受体协调不同的信号反应，发挥作用 细胞增殖和分化的重要调节因子，特别是在 发展。我们已经证明了该系统在II型细胞中的重要性。 差异化。发育细胞生物学的一个范例是细胞增殖 和分化处于机械性的张力中，这样一种 这一过程与另一过程的下调有关。在本建议书中 我们的假设是ErbB受体激活介导胎肺II型细胞 生长和分化，通过受体反应的多样化。我们会 解决三个具体目标：#1：控制II型细胞生长的机制 VS分化由不同的ErbB受体活性控制；#2： 利用ErbB调控胎儿II型细胞生长和分化的机制 每个过程特有的受体二聚体；以及#3：确定ErbB的作用 受体核定位在调节胎儿II型细胞生长中的作用 差异化。对胎儿II型细胞调控机制的新认识 增长将有助于我们开发新的治疗策略， 促进早产或其他发育不良后的正常肺发育 肺部疾病。

项目成果

ErbB4 is an upstream regulator of TTF-1 fetal mouse lung type II cell development in vitro.

ErbB4 是 TTF-1 胎儿小鼠肺 II 型细胞体外发育的上游调节因子。

• DOI: 10.1016/j.bbamcr.2013.06.030
• 发表时间: 2013
• 期刊: Biochimica et biophysica acta
• 作者: Zscheppang,Katja;Giese,Ulrike;Hoenzke,Stefan;Wiegel,Dorothea;Dammann,ChristianeEL
• 通讯作者: Dammann,ChristianeEL

Response to "Commentary on identity of fibroblast pneumocyte factor: rat vs. human".

对“成纤维细胞肺细胞因子身份的评论：大鼠与人类”的回应。

• DOI: 10.1038/pr.2017.86
• 发表时间: 2017
• 期刊: Pediatric research
• 影响因子: 3.6
• 作者: Nielsen,HeberC;King,George;Cake,MaxH
• 通讯作者: Cake,MaxH