PLK1 Regulation of Airway Smooth Muscle

PLK1 对气道平滑肌的调节

基本信息

批准号：
10609475
负责人：
Dale D. Tang
金额：
$ 48.36万
依托单位：
ALBANY MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10609475
关键词：
Actins Affect Allergens Asthma Binding Proteins Biological Process Biosensor Biotechnology Cell Extracts Cell Proliferation Cell Survival Cell physiology Cells Characteristics Complex Confocal Microscopy Cytoskeletal Proteins Cytoskeleton Data Development Disease Enzymes Extracellular Matrix Proteins Extrinsic asthma FRAP1 gene Gene Expression Regulation Goals Grant Growth Growth Factor Human Immunoprecipitation In Vitro Intermediate Filament Proteins Knockout Mice Knowledge Laboratories Lipids Malignant Neoplasms Mass Spectrum Analysis Mediating Muscle Contraction Nerve PLK1 gene Pathogenesis Pathologic Pathologic Processes Pathology Pathway interactions Persons Phosphorylation Phosphotransferases Pilot Projects Play Process Proliferating Protein Kinase Protein-Serine-Threonine Kinases Proteins Regulation Research Research Project Grants Role Sampling Signal Transduction Smooth Muscle Smooth Muscle Myocytes Structure System Testing Translations United States Universities airway hyperresponsiveness asthmatic asthmatic airway smooth muscle cancer cell cell type comparison control cytokine functional genomics in vivo knock-down nestin protein novel therapeutics polo-like kinase kinase 1 protein expression respiratory smooth muscle stem stem cell function tool

项目摘要

The contractility and growth of airway smooth muscle play an important role in the pathogenesis of airway hyperresponsiveness and smooth muscle layer thickening, cardinal features of asthma that affects nearly 250-300 million people worldwide. The mechanisms underlying these biological and pathological processes are not fully elucidated. Nestin is a type VI intermediate filament protein that has been implicated in progenitor cell functions and cancer pathogenesis. The functional role of nestin in airway smooth muscle is largely unknown. Pilot studies have shown that nestin may contribute to the regulation of smooth muscle contraction and proliferation. In Aim 1, we will determine the role of nestin in regulating airway smooth muscle contractility and cytoskeletal signaling. In Aim 2, we will assess the role and mechanism of nestin in airway smooth muscle proliferation and the growth factor-mediated pathways. In Aim 3, the potential role of nestin-associated cellular processes in human asthma will be determined. The role of nestin in allergen-induced asthma will also be evaluated in vivo. Completion of these studies should advance our knowledge regarding functional role and mechanism of nestin and cytoskeletal signaling in smooth muscle contractility and growth in vitro, and asthma pathogenesis in vivo. Obtaining this knowledge will facilitate the development of new therapy to treat asthma.

气道平滑肌的收缩和生长在气道高反应性和平滑肌层增厚的发病机理，哮喘的基本特征影响了全球近2.3亿人。这这些生物学和病理过程的基础机制尚未完全阐明。 Nestin是VI型中间细丝蛋白，已与祖细胞功能和癌症发病机理。 Nestin在气道中的功能作用平滑肌在很大程度上未知。试点研究表明，Nestin可能有助于调节平滑肌收缩和增殖。在AIM 1中，我们将确定Nestin在调节气道平滑肌收缩性和细胞骨架信号传导。在AIM 2中，我们将评估Nestin在气道平滑肌增殖和生长因子介导的途径。在AIM 3中，与巢蛋白相关的细胞过程在人哮喘中的潜在作用将是决定。 Nestin在过敏原诱导的哮喘中的作用也将在体内评估。这些研究的完成应提高我们对功能角色的了解和巢蛋白和细胞骨架信号的机制和平滑肌收缩性中的细胞骨架信号传导体外生长和体内哮喘发病机理。获得这些知识将有助于开发用于治疗哮喘的新疗法。