دورية أكاديمية
Pharmacological Inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis in Mice Cardiac Fibroblast and Post-Myocardial-Infarction Models
| العنوان: | Pharmacological Inhibition of Focal Adhesion Kinase Attenuates Cardiac Fibrosis in Mice Cardiac Fibroblast and Post-Myocardial-Infarction Models |
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| المؤلفون: | Guang-Pu Fan, Wei Wang, Hui Zhao, Lin Cai, Pei-De Zhang, Zi-He Yang, Jing Zhang, Xu Wang |
| المصدر: | Cellular Physiology and Biochemistry, Vol 37, Iss 2, Pp 515-526 (2015) |
| بيانات النشر: | Cell Physiol Biochem Press GmbH & Co KG, 2015. |
| سنة النشر: | 2015 |
| المجموعة: | LCC:Physiology LCC:Biochemistry |
| مصطلحات موضوعية: | Focal adhesion kinase, Cardiac fibroblasts, Cardiac fibrosis, PF-562,271, Myocardial infarction, Physiology, QP1-981, Biochemistry, QD415-436 |
| الوصف: | 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 (pConclusion: This study provides novel evidence that FAK inhibition may become a promising pharmaceutical strategy to attenuate fibrosis post-MI. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1015-8987 1421-9778 |
| Relation: | http://www.karger.com/Article/FullText/430373; https://doaj.org/toc/1015-8987; https://doaj.org/toc/1421-9778 |
| DOI: | 10.1159/000430373 |
| URL الوصول: | https://doaj.org/article/883b3cb256014aedacac927ed99d4a01 |
| رقم الأكسشن: | edsdoj.883b3cb256014aedacac927ed99d4a01 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 10158987 14219778 |
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| DOI: | 10.1159/000430373 |