Focal Adhesion Kinase and FAK-related Non-kinase in Idiopathic Pulmonary Fibrosis

描述（由申请人提供）： 特发性肺纤维化（IPF）是一种慢性肺部疾病，可导致进行性呼吸功能不全和肺纤维化，并伴有致死性结局。IPF的发病机制尚不清楚。目前，没有有效的治疗方法来治愈IPF。表征IPF发病机制中涉及的分子途径对于开发IPF患者的新型靶向治疗方法至关重要。粘着斑激酶（FAK）是一种酪氨酸激酶，在细胞迁移、增殖/存活和肌成纤维细胞分化中起关键作用。FAK相关非激酶（FRNK）是FAK介导的细胞迁移和肌成纤维细胞分化的内源性抑制剂。为了研究FRNK在IPF患者肺纤维化发展中的作用，提出了两个具体目标。该建议将检查FRNK和FAK的表达，以及FAK和下游介质的激活。将分析拟定研究的结果与IPF患者肺纤维化严重程度的相关性。这些研究结果将为FRNK在肺纤维化发展中的作用提供新的见解，并为进一步的机制研究奠定基础。公共卫生相关性：这些研究将为FAK相关非激酶在人类肺纤维化发展中的作用提供新的见解。 (End摘要）

DESCRIPTION (provided by applicant): Idiopathic pulmonary fibrosis (IPF) is a chronic lung disorder resulting in progressive respiratory insufficiency and lung fibrosis with fatal outcome. The pathogenesis of IPF remains unclear. Currently, there is no effective therapy to cure IPF. Characterization of molecular pathways involved in the pathogenesis of IPF is essential to develop novel targeted therapeutic approaches for IPF patients. Focal adhesion kinase (FAK) is a tyrosine kinase and plays a critical role in cell migration, proliferation/survive, and myofibroblast differentiation. FAK-related non-kinase (FRNK) is an endogenous inhibitor of FAK-mediated cell migration and myofibroblast differentiation. To investigate the role of FRNK in the development of lung fibrosis in IPF patients, two specific aims are proposed. This proposal will examine the FRNK and FAK expression, and the activation of FAK and downstream mediators. The findings from the proposed studies will be analyzed for the correlation with the severity of lung fibrosis in IPF patients. The findings of the proposed studies will provide new insights regarding the role of FRNK in the development of lung fibrosis, and serve as the basis for further mechanistic studies. PUBLIC HEALTH RELEVANCE: The proposed studies will provide new insights regarding the role of FAK-related Non- kinase in the development of pulmonary fibrosis in human. (End of Abstract)