Plk1 Regulation of Airway Smooth Muscle

Plk1 气道平滑肌的调节

基本信息

批准号：
9304309
负责人：
Dale D. Tang
金额：
$ 39.5万
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 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9304309
关键词：
Actins Adaptor Signaling Protein Affect Affinity Allergens Animal Model Asthma Attenuated Biological Biological Assay Biosensor Cell Proliferation Cell division Cell physiology Cells Characteristics Contracts Cytokinesis Cytoskeletal Proteins Development Disease Extrinsic asthma Filament Goals Growth Human In Vitro Inflammation Intermediate Filament Proteins Knockout Mice Knowledge Laboratories Lung diseases Mediating MicroRNAs Microfilaments Mitosis Molecular Muscle Cells Muscle Contraction PLK1 gene Pathogenesis Pathology Phosphorylation Pilot Projects Play Precipitation Process Proliferating Protein-Serine-Threonine Kinases Proteins Reagent Regulation Research Role Smooth Muscle Smooth Muscle Myocytes Subfamily lentivirinae Technology Testing Tissues Vimentin airway hyperresponsiveness airway inflammation airway remodeling asthmatic asthmatic airway in vivo knock-down novel therapeutics paxillin respiratory smooth muscle response self assembly small hairpin RNA stem tool transmission process

项目摘要

Asthma is a serious lung disease that affects nearly 20 million people in the United Sates and 250 million people worldwide. Airway hyperresponsiveness (AHR) and airway remodeling are cardinal characteristics of asthma. It is known that airway smooth muscle contraction plays a critical role in mediating AHR whereas airway smooth muscle cell proliferation largely contributes to the pathogenesis of airway remodeling. However, the mechanisms that regulate airway smooth muscle contraction and growth are not well understood. Polo-like kinase 1 (Plk1) is a serine/threonine protein kinase that has been implicated mitosis of nonmuscle cells. The functional role of Plk1 in smooth muscle is currently unknown. Our pilot studies have shown that Plk1 is involved in the regulation of airway smooth muscle contraction and cytokinesis, a key step of cell proliferation. The major goal of the project is to unveil the role of Plk1 in airway smooth muscle contraction and cytokinesis in vitro, and the pathogenesis of AHR and airway remodeling in vivo. In Aims 1 and 2, the role and mechanisms of Plk1 in airway smooth muscle contraction and cytokinesis will be characterized. In Aim 3, the role of Plk1 in allergen-induced AHR, airway remodeling and airway inflammation will be assessed using animal models of asthma. Completion of these studies should advance our knowledge regarding smooth muscle contraction/cytokinesis and asthma pathology. Obtaining this knowledge may identify Plk1 as a new biological target for the development of new therapy to treat asthma.

哮喘是一种严重的肺部疾病，影响着近 2000 万人美国和全世界 2.5 亿人。气道高反应性 (AHR) 和气道重塑是哮喘的主要特征。众所周知，气道通畅肌肉收缩在介导 AHR 中起着关键作用，而气道平滑肌细胞增殖在很大程度上促进了气道重塑的发病机制。然而，调节气道平滑肌收缩和生长的机制并不完善明白了。 Polo 样激酶 1 (Plk1) 是一种丝氨酸/苏氨酸蛋白激酶，已被涉及非肌肉细胞的有丝分裂。 Plk1在平滑肌中的功能作用是目前未知。我们的试点研究表明 Plk1 参与调节气道平滑肌收缩和胞质分裂，这是细胞增殖的关键步骤。这该项目的主要目标是揭示 Plk1 在气道平滑肌收缩中的作用体外和胞质分裂，以及体内 AHR 和气道重塑的发病机制。在目标1和2，Plk1在气道平滑肌收缩和收缩中的作用和机制将表征胞质分裂。在目标 3 中，Plk1 在过敏原诱导的 AHR 中的作用，将使用动物模型评估气道重塑和气道炎症哮喘。完成这些研究应该会提高我们关于顺利进行的知识肌肉收缩/细胞分裂和哮喘病理学。获得这些知识可能确定 Plk1 作为开发新疗法的新生物靶点哮喘。