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：
9326335
负责人：
Thomas Harrison Barker
金额：
$ 67.6万
依托单位：
UNIVERSITY OF VIRGINIA
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 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9326335
关键词：
Actins Address Affect Affinity American Architecture Atherosclerosis Automobile Driving Biochemical Biological Biological Process Biology Biomechanics Biophysics Buffers Cells Cicatrix Clinical Development Diagnosis Diagnostic Disease Disease Management Disease Progression Elements Embryology Engineering Extracellular Matrix FDA approved Feedback Fibroblasts Fibrosis Foundations Genes Genetic Transcription Goals Hamman-Rich syndrome Health Human Impairment 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 Viral Load result Wound Healing conventional therapy in vivo innovation insight killings malignant breast neoplasm mechanotransduction 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 (IPF) 是一种影响多达 500,000 名美国人的绝症，目前尚无 FDA 批准的能够阻止疾病进展的疗法。该疾病的特征是细胞外基质 (ECM) 过度组装。激活的成纤维细胞被称为“肌成纤维细胞”，最近的研究表明，组织力学，特别是由肌成纤维细胞组装而成的组织硬度。简而言之，肌成纤维细胞能够募集更多的肌成纤维细胞，导致疾病不受控制地进展，但我们仍然不了解该过程是如何启动的。然而，我们已经开发并确定了细胞如何“感知”这种僵硬（“机械传感”）的任何疗法。相同的细胞机制使他们能够感知增加的硬度，以开发用于提供局部疤痕定向治疗的技术，其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机械传感基础的科学见解。细胞并选择自然发生的范式来使疾病状态对抗自身。