scholarly journals Focal Adhesion Kinase Is Upstream of Phosphatidylinositol 3-Kinase/Akt in Regulating Fibroblast Survival in Response to Contraction of Type I Collagen Matrices via a β1Integrin Viability Signaling Pathway

2004 ◽  
Vol 279 (31) ◽  
pp. 33024-33034 ◽  
Author(s):  
Hong Xia ◽  
Richard Seonghun Nho ◽  
Judy Kahm ◽  
Jill Kleidon ◽  
Craig A. Henke
Keyword(s):  
Focal Adhesion Kinase ◽  
Signaling Pathway ◽  
Focal Adhesion ◽  
Type I Collagen ◽  
Type I ◽  
Phosphatidylinositol 3 Kinase ◽  
Collagen Matrices ◽  
Phosphatidylinositol 3

Identification of focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3-kinase) as Par3 partners by proteomic analysis

Cytoskeleton ◽  
2010 ◽  
pp. NA-NA ◽  
Author(s):  
Norimichi Itoh ◽  
Masanori Nakayama ◽  
Takashi Nishimura ◽  
Shin Fujisue ◽  
Tomoki Nishioka ◽  
...  
Keyword(s):  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Proteomic Analysis ◽  
Pi3 Kinase ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

scholarly journals Pharmacological Inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis in Mice Cardiac Fibroblast and Post-Myocardial-Infarction Models

2015 ◽  
Vol 37 (2) ◽  
pp. 515-526 ◽  
Author(s):  
Guang-Pu Fan ◽  
Wei Wang ◽  
Hui Zhao ◽  
Lin Cai ◽  
Pei-De Zhang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Cardiac Fibrosis ◽  
Type I Collagen ◽  
Heart Function ◽  
Smooth Muscle Actin ◽  
Post Myocardial Infarction ◽  
Type I ◽  
Pharmacological Inhibition

Background: To investigate the role of focal adhesion kinase (FAK)-mediated signaling in hypoxia-induced cardiac fibroblasts (CFs) differentiation and cardiac fibrosis post-myocardial infarction (MI) on a mice model. Methods: CFs of neonatal C57BL/6 mice were treated under normoxic, hypoxic, or hypoxic+PP2 (known as a Src kinase family inhibitor) conditions. Gene expressions of FAK, alpha-smooth muscle actin (α-SMA) and collagen type I alpha 1 (Col1α1), or α-SMA and vimentin levels were performed by RT-PCR and immunofluorescence staining, respectively. Thirty mice were surgically treated into Sham (n=7) and MI (n=23) groups; and FAK inhibitor PF-562271 was given to six survivor MI mice (as PF group, from 15 survivors). Heart function and collagenous tissues were examined by echocardiography, as well as by Masson‘s trichrome and Sirius red staining, respectively. Type I collagen, FAK protein, mTOR, ERK1/2, AKT, P70S6K and phospho-FAK levels were also analyzed. Results: FAK inhibition with PP2 significantly decreased CFs differentiation and collagen synthesis under hypoxia treatment. In vivo, PF-562271 treatment resulted in fibrosis attenuation; however, deteriorated heart function of MI mice could not be significantly improved. PF-562271 may affect phospho-mTOR (p<0.05), phospho-ERK1/2 (p<0.01), phospho-AKT (p<0.001) and phospho-P70S6K (p<0.05) to exert its benefits. FAK can be activated either under hypoxia in CFs or MI in a mouse model to promote fibrosis. However, pharmacological inhibition of FAK can attenuate fibrosis response. Conclusion: This study provides novel evidence that FAK inhibition may become a promising pharmaceutical strategy to attenuate fibrosis post-MI.

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