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Mechanosensors that detect and treat Lung Fibrosis

检测和治疗肺纤维化的机械传感器

基本信息

批准号：
8949230
负责人：
Thomas Harrison Barker
金额：
$ 69.16万
依托单位：
GEORGIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-07 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8949230
关键词：
Actins Address Affect Affinity American Architecture Atherosclerosis Automobile Driving Biochemical Biological Biological Process Biology Biomechanics Buffers Cells Cicatrix Clinical Development Diagnosis Diagnostic Disease Disease Management Disease Progression Elements Embryology Engineering Extracellular Matrix FDA approved Feedback Fibroblasts Fibrosis Genes Goals Hamman-Rich syndrome Health Human In Vitro Intervention Libraries Link Local Therapy Lung Lung Compliance Lung Transplantation Malignant Neoplasms Maps Mechanics Medical Medicine Molecular Mus Myofibroblast Names Neoplasm Metastasis Outcome Pathologic Pathology Pathway interactions Patients Physiological Process Protease Inhibitor Pulmonary Fibrosis Recruitment Activity Reporter Reporting Rest Role Signal Transduction Stimulus System Technology Terminal Disease Therapeutic Tissues Transgenic Organisms Wound Healing base conventional therapy effective therapy in vivo innovation insight killings malignant breast neoplasm promoter public health relevance response sensor stem cell differentiation technology development therapeutic target tissue regeneration transcription factor

项目摘要

DESCRIPTION (provided by applicant): Idiopathic Pulmonary Fibrosis, or IPF, is a terminal disease affecting as many as 500,000 Americans with no FDA-approved therapies capable of stopping disease progression. The disease is characterized by excessive assembly of extracellular matrix (ECM) by activated fibroblasts termed `myofibroblasts'. Recently, studies have demonstrated that tissue mechanics, specifically tissue stiffness resulting from myofibroblasts assembly of ECM and contraction, is capable of driving the differentiation of myofibroblasts and thus disease progression. In short, myofibroblasts are capable of recruiting more myofibroblasts leading to a disease that progresses unchecked. Despite these recent findings we still do not understand how the process is initiated, nor do we have any therapies that effective halt disease progression. Basic molecular mechanisms for how cells "sense" this stiffness ("mechano-sensing") have, however, been developed and identified. In this project we are harnessing the same cellular mechanisms that allow them to sense the increased stiffness toward the development of technology for delivering local, scar-directed therapy with the goal of treating and curing pulmonary fibrosis directly. This approach leverages years of scientific insight into the basis for mechanical sensing by cells and co-opts naturally occurring paradigms to turn the disease state against itself.

描述（由申请人提供）：特发性肺纤维化或IPF是一种影响多达50万美国人的终末期疾病，没有FDA批准的能够阻止疾病进展的治疗。该疾病的特征在于细胞外基质（ECM）被称为“肌成纤维细胞”的活化成纤维细胞过度组装。最近，研究已经证明，组织力学，特别是由ECM的肌成纤维细胞组装和收缩引起的组织硬度，能够驱动肌成纤维细胞的分化，从而驱动疾病进展。简而言之，肌成纤维细胞能够招募更多的肌成纤维细胞，导致疾病不受控制地进展。尽管有这些最新的发现，我们仍然不知道这个过程是如何开始的，我们也没有任何有效阻止疾病进展的疗法。然而，细胞如何“感知”这种硬度（“机械感知”）的基本分子机制已经开发和鉴定。在这个项目中，我们正在利用相同的细胞机制，使他们能够感知到增加的刚度，以开发用于提供局部，瘢痕导向治疗的技术，目标是直接治疗和治愈肺纤维化。这种方法利用了多年来对细胞机械传感基础的科学见解，并选择了自然发生的范例来改变疾病状态。