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.
The proposed studies will provide new insights regarding the role of FAK-related Non- kinase in the development of pulmonary fibrosis in human.
| Wagener, Brant M; Hu, Meng; Zheng, Anni et al. (2016) Neuronal Wiskott-Aldrich syndrome protein regulates TGF-?1-mediated lung vascular permeability. FASEB J 30:2557-69 |
| Ding, Qiang; Cai, Guo-Qiang; Hu, Meng et al. (2013) FAK-related nonkinase is a multifunctional negative regulator of pulmonary fibrosis. Am J Pathol 182:1572-84 |
| Cai, Guo-Qiang; Chou, Chu-Fang; Hu, Meng et al. (2012) Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is critical for formation of ?-smooth muscle actin filaments during myofibroblast differentiation. Am J Physiol Lung Cell Mol Physiol 303:L692-702 |
| Zhan, Shuqin; Cai, Guo-Qiang; Zheng, Anni et al. (2011) Tumor necrosis factor-alpha regulates the Hypocretin system via mRNA degradation and ubiquitination. Biochim Biophys Acta 1812:565-71 |
| Cai, Guo-qiang; Zheng, Anni; Tang, Qingjiu et al. (2010) Downregulation of FAK-related non-kinase mediates the migratory phenotype of human fibrotic lung fibroblasts. Exp Cell Res 316:1600-9 |
