Mechanosensors that detect and treat Lung Fibrosis

 描述(申请人提供)：特发性肺纤维化，或IPF，是一种晚期疾病，影响多达50万美国人，没有FDA批准的能够阻止疾病进展的治疗方法。这种疾病的特征是激活的成纤维细胞过度聚集细胞外基质(ECM)，称为肌成纤维细胞。最近的研究表明，组织力学，特别是肌成纤维细胞组装ECM和收缩所产生的组织硬度，能够驱动肌成纤维细胞的分化，从而推动疾病的进展。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发展。尽管有这些最近的发现，我们仍然不知道这个过程是如何启动的，我们也没有任何有效阻止疾病进展的治疗方法。然而，细胞如何“感觉”这种僵硬(“机械感觉”)的基本分子机制已经被开发和识别。在这个项目中，我们正在利用相同的细胞机制，使他们能够感受到随着技术的发展而增加的僵硬，以提供局部、疤痕定向治疗，目标是直接治疗和治疗肺纤维化。这种方法利用多年来对细胞机械感知基础的科学洞察力，并利用自然发生的范例来使疾病状态对其自身不利。

 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.