Taipei Medical University

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Wang TL
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------>journal_name=J Mol Cell Cardiol
------>paper_name=Angiotensin II Signals Mechanical Stretch-Induced Cardiac Matrix Metalloproteinase Expression via JAK-STAT Pathway
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------>fullAbstract=BACKGROUND: Mechanical stress induces many pathophysiological effects in cardiomyocytes. The objective of this study was to test the hypothesis that angiotensin II is a potential mediator of stretch-induced activation of matrix metalloproteinases (MMP). METHODS: Neonatal rat cardiomyocytes grown on a flexible membrane were cyclically stretched achieving up to 20% elongation at 60 cycles/min (using a vacuum). We explored the signaling pathways involved in cyclical stretch-induced expression of MMP-14 and MMP-2. RESULTS: Cyclical mechanical stretch significantly increased mRNA expression and protein synthesis for MMP-14 and MMP-2 from the 6(th) to 24(th) h. The increase in MMP-14 and -2 proteins after stretch was completely blocked after the pretreatment with losartan (an angiotensin II AT1 receptor antagonist, 200 nM) and AG-490 (a Janus kinase 2 tyrosine kinase inhibitor, 100 nM) but not with PD 98059 (an inhibitor of p42/p44 mitogen-activated protein kinase, 50 microM) or wortmannin (a phosphatidylinositol 3-kinase, 30 nM). By zymography, MMP-2 activity was increased by cyclical stretch that was significantly attenuated by losartan and AG-490. The mechanical strain also increased the immunohistochemical labeling of MMP-14 and -2 that was attenuated by adding losartan. Cyclical stretch increased the expression of STAT-1 that was abolished by pretreating with losartan or AG-490 (50 microM and 100 microM). CONCLUSION: These findings indicate that cyclical stretch induces MMP-14 and -2 expression in neonatal rat cardiomyocytes and that the induction is mediated by the angiotensin II-JAK-STAT1 pathway.
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------>authors2=Yang YH
------>authors3=Chang H
------>authors4=Hung CR
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------>authors=Wang TL
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------>updateTitle=Angiotensin II signals mechanical stretch-induced cardiac matrix metalloproteinase expression via JAK-STAT pathway.
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------>no=3
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------>publish_year=2004
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------>publish_month=9
A B C D E F G H I J K L M N O P Q R S T U V W X Y Z