Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Exp Cell Res. 2010 May 15;316(9):1600-9. doi: 10.1016/j.yexcr.2010.01.021. Epub 2010 Jan 25.
Fibroblast migration plays an important role in the normal wound healing process; however, dysregulated cell migration may contribute to the progressive formation of fibrotic lesions in the diseased condition. To examine the role of focal-adhesion-kinase (FAK)-related non-kinase (FRNK) in regulation of fibrotic lung fibroblast migration, we examined cell migration, FRNK expression, and activation of focal adhesion kinase (FAK) and Rho GTPase (Rho and Rac) in primary lung fibroblasts derived from both idiopathic pulmonary fibrosis (IPF) patients and normal human controls. Fibrotic (IPF) lung fibroblasts have increased cell migration when compared to control human lung fibroblasts. FRNK expression is significantly reduced in IPF lung fibroblasts, while activation of FAK, Rho and Rac is increased in IPF lung fibroblasts. Endogenous FRNK expression is inversely correlated with FAK activation and cell migration rate in IPF lung fibroblasts. Forced exogenous FRNK expression abrogates the increased cell migration, and blocked the activation of FAK and Rho GTPase (Rho and Rac), in IPF lung fibroblasts. These data for the first time provide evidence that downregulation of endogenous FRNK plays a role in promoting cell migration through FAK and Rho GTPase in fibrotic IPF lung fibroblasts.
成纤维细胞迁移在正常伤口愈合过程中起着重要作用；然而，细胞迁移失调可能导致疾病状态下纤维性病变的进行性形成。为了研究粘着斑激酶（FAK）相关非激酶（FRNK）在调节纤维性肺成纤维细胞迁移中的作用，我们检测了原代肺成纤维细胞的细胞迁移、FRNK 表达以及粘着斑激酶（FAK）和 Rho GTPase（Rho 和 Rac）的激活情况，这些细胞来源于特发性肺纤维化（IPF）患者和正常人类对照。与正常肺成纤维细胞相比，纤维化（IPF）肺成纤维细胞的细胞迁移增加。IPF 肺成纤维细胞中 FRNK 的表达显著降低，而 FAK、Rho 和 Rac 的激活增加。内源性 FRNK 的表达与 IPF 肺成纤维细胞中 FAK 的激活和细胞迁移率呈负相关。强制外源性 FRNK 表达可阻断 IPF 肺成纤维细胞中细胞迁移的增加，并阻断 FAK 和 Rho GTPase（Rho 和 Rac）的激活。这些数据首次提供了证据，证明内源性 FRNK 的下调通过 FAK 和 Rho GTPase 在纤维性 IPF 肺成纤维细胞中促进细胞迁移。
