Stress and Vascular Responses: Mitogen-Activated Protein Kinases and Activator Protein-1 as Promising Therapeutic Targets of Vascular Remodeling
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概要
- 論文の詳細を見る
Mitogen-activated protein kinases (MAP kinases), including extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38, play a central role in cellular responses by various stress stimuli such as cell proliferation, apoptosis, migration, or gene expression. Furthermore, activator protein-1 (AP-1), a transcription factor which can be activated by MAP kinases, also is involved in a variety of celllar responses, as well as MAP kinases. MAP kinases and AP-1 are significantly activated in vascular tissues by hypertension, angiotensin II, or balloon injury. We have made dominant negative mutants of MAP kinases or c-Jun, to specifically inhibit in vivo activation of MAP kinases or AP-1. Vascular gene transfer of each dominant negative mutant of MAP kinases or c-Jun prevents intimal hyperplasia after balloon injury, which is associated with the inhibition of smooth muscle cell proliferation in the intima and the media and probably also associated with inhibition of smooth muscle cell migration. However, in vitro findings on cultured vascular smooth muscle cells suggest that the molecular mechanism underlying inhibition of intimal hyperplasia may be different among each dominant negative mutant of MAP kinases and c-Jun. MAP kinases and c-Jun seem to be the promising therapeutic target for vascular remodeling.
- 社団法人 日本薬理学会の論文
- 2003-03-01
著者
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IWAO Hiroshi
Department of Pharmacology, Osaka City University School of Medicine
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KIM Shokei
Department of Pharmacology, Osaka City Unitersity Medical School
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Kim Shokei
Department Of Pharmacology Osaka City University Medical School
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Iwao Hiroshi
Department Of Pharmacology Graduate School Of Medicine Osaka City University
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Kim Shokei
Department Of Pharmacolgy Osaka City Unversity Medical School
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Iwao Hiroshi
Department Of Cardiovascular Medicine Akita University Graduate School Of Medicine
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Kim Shokei
Department Of Internal Medicine And Cardiology Osaka City University Medical School
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