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Cardiac fibroblasts require focal adhesion kinase for normal proliferation and migration

Authors
 Ana Maria Manso  ;  Seok-Min Kang  ;  Sergey V. Plotnikov  ;  Ingo Thievessen  ;  Jaewon Oh  ;  Hilary E. Beggs  ;  Robert S. Ross 
Citation
 AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, Vol.296(3) : 627-38, 2009 
Journal Title
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
ISSN
 0363-6135 
Issue Date
2009
MeSH
Animals ; Cell Adhesion ; Cell Movement* ; Cell Proliferation* ; Cell Shape ; Cells, Cultured ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Fibroblasts/enzymology* ; Focal Adhesion Kinase 1/deficiency ; Focal Adhesion Kinase 1/genetics ; Focal Adhesion Kinase 1/metabolism* ; Focal Adhesion Kinase 2/metabolism ; Focal Adhesions/metabolism ; JNK Mitogen-Activated Protein Kinases/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myocardium/cytology ; Myocardium/enzymology* ; Paxillin/metabolism ; Platelet-Derived Growth Factor/metabolism ; Protein-Tyrosine Kinases/metabolism ; Proto-Oncogene Proteins c-sis ; Talin/metabolism ; Time Factors ; Vinculin/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism
Keywords
extracellular matrix ; cytoskeleton ; fibroblast
Abstract
Migration and proliferation of cardiac fibroblasts (CFs) play an important role in the myocardial remodeling process. While many factors have been identified that regulate CF growth and migration, less is known about the signaling mechanisms involved in these processes. Here, we utilized Cre-LoxP technology to obtain focal adhesion kinase (FAK)-deficient adult mouse CFs and studied how FAK functioned in modulating cell adhesion, proliferation, and migration of these cells. Treatment of FAK(flox/flox) CFs with Ad/Cre virus caused over 70% reduction of FAK protein levels within a cell population. FAK-deficient CFs showed no changes in focal adhesions, cell morphology, or protein expression levels of vinculin, talin, or paxillin; proline-rich tyrosine kinase 2 (Pyk2) expression and activity were increased. Knockdown of FAK protein in CFs increased PDGF-BB-induced proliferation, while it reduced PDGF-BB-induced migration. Adhesion to fibronectin was not altered. To distinguish between the function of FAK and Pyk2, FAK function was inhibited via adenoviral-mediated overexpression of the natural FAK inhibitor FAK-related nonkinase (FRNK). Ad/FRNK had no effect on Pyk2 expression, inhibited the PDGF-BB-induced migration, but did not change the PDGF-BB-induced proliferation. FAK deficiency had only modest effects on increasing PDGF-BB activation of p38 and JNK MAPKs, with no alteration in the ERK response vs. control cells. These results demonstrate that FAK is required for the PDGF-BB-induced migratory response of adult mouse CFs and suggest that FAK could play an essential role in the wound-healing response that occurs in numerous cardiac pathologies.
Files in This Item:
T200900586.pdf Download
DOI
10.1152/ajpheart.00444.2008
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Min(강석민) ORCID logo https://orcid.org/0000-0001-9856-9227
Oh, Jae Won(오재원) ORCID logo https://orcid.org/0000-0002-4585-1488
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103528
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