The Vagus Nerve in Lung Disease

肺部疾病中的迷走神经

• 批准号: 10592236
• 负责人: JERRY (Jun) YU
• 金额: --
• 依托单位: LOUISVILLE VA MEDICAL MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10592236
• 关键词: Acetylcholine; Acute Respiratory Distress Syndrome; Address; Adoptive Cell Transfers; Agonist; Asthma; Attenuated; Biochemical; Biochemistry; Biological; Biosensor; Brain; Bronchoalveolar Lavage; Cell Count; Cells; Cessation of life; Chronic; Chronic Obstructive Pulmonary Disease; Cicatrix; Collagen; Complex; Cytology; Data; Deposition; Development; Disease; Dyspnea; Endothelial Cells; Epithelial Cells; Fibroblasts; Fibrosis; Gases; Gene Expression; Growth Factor; Histology; Hospitals; Immune response; Inflammatory; Injury; Lead; Lung; Lung diseases; Malignant neoplasm of lung; Mammals; Mediating; Mediator of activation protein; Molecular; Mus; Myofibroblast; Nerve; Nerve Block; Neural Pathways; Neuraxis; Neuroendocrine Cell; Neuroepithelial Bodies; Neuroimmune; Neurosecretory Systems; Outcome; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Pharmacology; Phase; Physiology; Plasma; Play; Process; Pulmonary Fibrosis; Pulmonary Inflammation; Research; Respiratory Mucosa; Role; Sensory Receptors; Severities; System; Techniques; Testing; Transforming Growth Factor beta; Vagotomy; Vagus nerve structure; antagonist; chemical release; cytokine; effective therapy; fibrogenesis; fibrotic lung disease; genetic manipulation; improved; indium-bleomycin; lung development; lung injury; lung repair; military veteran; mouse model; neuromechanism; novel; novel strategies; patient population; protein expression; receptor; recruit; sensor; stem cells; vagus nerve stimulation

Pulmonary neuroendocrine (PNECs) cells are widely distributed throughout the airway mucosa. These cells can be solitary or aggregated to form neuroepithelial bodies (NEBs), which are richly innervated by the vagus nerve. PNECs/NEBs are important for early phases of lung development and also associated with stem cell niches in the airways. They are airway sensors. Airway sensory receptors are biosensors that detect lung inflammation and injury through various mediators and cytokines. This information is transmitted through vagal afferents to the brain and produces a host of responses that regulate the pathophysiological process. Increasing evidence suggests that the vagus nerve plays an important role in a variety of pulmonary diseases from asthma, COPD, ARDS to lung cancer. Pulmonary fibrosis (PF) can result from a variety of insults to the lung. Lung repair following an insult-induced injury is a complex process involving both resident cells and recruited cells. The progression of PF results from a network of interactions among mediators, cytokines, and growth factors derived from inflammatory, endothelial, and epithelial cells, which leads to lung remodeling, deposition of collagen, limitation of gas exchange, and dyspnea. The vagus nerve is closely related to each component of this network, thus its function may influence the outcome of PF. Since lung injury is a major component in the development of PF and harmful insults to the lung may stimulate the NEB-Vagal System (NVS), a novel hypothesis that activation of the NVS promotes lung fibrosis will be tested. [If this hypothesis is correct, suppression of the NVS should attenuate fibrosis, whereas stimulation of the NVS should promote fibrosis. By examining lung fibrosis in bleomycin treated mice in which the NVS is either stimulated or suppressed (vagotomy, medication, gene manipulation, or cell adoptive transfer), and by assessing well-established cellular and molecular pathways that lead to PF with different techniques (histology, physiology, cytology and biochemistry), the underlying neural mechanisms will be delineated.] Successful completion of the studies will establish a novel neural mechanism in the pathogenesis of PF. [This potentially may lead to a new pharmacological approach to treat or to limit chronic fibrotic diseases in the Veteran population.]

肺神经内分泌（PNEC）细胞广泛分布 气道粘膜。这些细胞可以单独或聚集以形成神经上皮 身体（NEB），被迷走神经支配。 PNEC/NEB是 对于肺发育的早期阶段很重要，也与干细胞有关 气道中的利基。它们是气道传感器。气道感觉受体是 通过各种介体和 细胞因子。这些信息是通过迷走神经传感传播到大脑的， 产生许多调节病理生理过程的反应。 越来越多的证据表明迷走神经在一个 从哮喘，COPD，ARDS到肺癌的各种肺部疾病。 肺纤维化（PF）可能是由于对肺部的多种侮辱而引起的。肺修复 侮辱性造成的伤害是一个涉及两个居民细胞的复杂过程 和招募的细胞。 PF的进展来自相互作用网络 在介体，细胞因子和炎症中得出的生长因子中， 内皮和上皮细胞，导致肺重塑，沉积 胶原蛋白，气体交换的限制和呼吸困难。迷走神经紧密 与该网络的每个组件相关，因此其功能可能会影响 PF的结果。由于肺损伤是PF发展的主要组成部分 对肺的有害侮辱可能会刺激NEB-VAGAL系统（NVS），这是一种小说 将测试NVS激活促进肺纤维化的假设。 [如果这个 假设是正确的，抑制NV应减弱纤维化，而 NV的刺激应促进纤维化。通过检查肺纤维化 刺激或抑制NVS的博来霉素处理的小鼠 （迷走神经切开术，药物，基因操纵或细胞收养转移），并通过 评估公认的细胞和分子途径，这些途径导致PF 不同的技术（组织学，生理学，细胞学和生物化学）， 将划定潜在的神经机制。]成功完成 研究将在PF发病机理中建立一种新的神经机制。 [这 可能会导致一种新的药理方法来治疗或限制慢性 退伍军人人口中的纤维化疾病。]