Document Detail


Cardiac fibroblasts require focal adhesion kinase for normal proliferation and migration.
MedLine Citation:
PMID:  19136609     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ana Maria Manso; Seok-Min Kang; Sergey V Plotnikov; Ingo Thievessen; Jaewon Oh; Hilary E Beggs; Robert S Ross
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-01-09
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  296     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-03-03     Completed Date:  2009-04-09     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H627-38     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of California-San Diego School of Medicine, La Jolla, California, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Adhesion
Cell Movement*
Cell Proliferation*
Cell Shape
Cells, Cultured
Extracellular Signal-Regulated MAP Kinases / metabolism
Fibroblasts / enzymology*
Focal Adhesion Kinase 1 / deficiency,  genetics,  metabolism*
Focal Adhesion Kinase 2 / metabolism
Focal Adhesions / metabolism
JNK Mitogen-Activated Protein Kinases / metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Myocardium / cytology,  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
Grant Support
ID/Acronym/Agency:
P01-HL-066941/HL/NHLBI NIH HHS; R01-HL-057872/HL/NHLBI NIH HHS; R01-HL-088390/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Paxillin; 0/Platelet-Derived Growth Factor; 0/Proto-Oncogene Proteins c-sis; 0/Pxn protein, mouse; 0/Talin; 0/platelet-derived growth factor BB; 125361-02-6/Vinculin; EC 2.7.1.-/FAK-related nonkinase; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.2/Focal Adhesion Kinase 1; EC 2.7.10.2/Focal Adhesion Kinase 2; EC 2.7.10.2/Ptk2 protein, mouse; EC 2.7.10.2/Ptk2b protein, mouse; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases
Comments/Corrections

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