文献类型： 外文期刊
作者： Ding, Qiang 1 ; Cai, Guo-qiang 1 ; Hu, Meng 1 ; Yang, Youfeng 1 ; Zheng, Anni 1 ; Tang, Qinjiu 2 ; Gladson, Candece L. 3 ;
作者机构： 1.Univ Alabama Birmingham, Dept Med, Div Pulm & Crit Care Med, Birmingham, AL 35294 USA
2.Shanghai Acad Agr Sci, Inst Edible Fungi, Shanghai, Peoples R China
3.Cleveland Clin, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44106 USA
4.Cleveland Clin, Lerner Res Inst, Dept Pathobiol, Cleveland, OH 44106 USA
5.Osaka Univ, Dept Immunodynam, Osaka, Japan
6.Tulane Univ, Dept M
期刊名称：AMERICAN JOURNAL OF PATHOLOGY （ 影响因子：4.307； 五年影响因子：5.138 ）
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收录情况： SCI
摘要： Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease whose underlying molecular mechanisms are largely unknown. Herein, we show that focal adhesion kinase-related nonkinase (FRNK) plays a key role in limiting the development of lung fibrosis. Loss of FRNK function in vivo leads to increased lung fibrosis in an experimental mouse model. The increase in lung fibrosis is confirmed at the histological, biochemical, and physiological levels. Concordantly, loss of FRNK function results in increased fibroblast migration and myofibroblast differentiation and activation of signaling proteins that drive these phenotypes. FRNK-deficient murine lung fibroblasts also have an increased capacity to produce and contract matrix proteins. Restoration of FRNK expression in vivo and in vitro reverses these profibrotic phenotypes. These data demonstrate the multiple antifibrotic actions of FRNK. More important, FRNK expression is down-regulated in human IPF, and down-regulation of FRNK in normal human lung fibroblasts recapitulates the profibrotic phenotype seen in FRNK-deficient cells. The effect of loss and gain of FRNK in the experimental model, when taken together with its down-regulation in human IPF, suggests that FRNK acts as an endogenous negative regulator of lung fibrosis by repressing multiple profibrotic responses.
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