Downregulation of FAK-related non-kinase mediates the migratory phenotype of human fibrotic lung fibroblasts.
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.
Cai
Guo-qiang
GQ
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Zheng
Anni
A
Tang
Qingjiu
Q
White
Eric S
ES
Chou
Chu-Fang
CF
Gladson
Candece L
CL
Olman
Mitchell A
MA
Ding
Qiang
Q
D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism
C113183:FAK-related nonkinase; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020741:rho GTP-Binding Proteins