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Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/3185

Title: Exendin-4 Prevents Vascular Smooth Muscle Cell Proliferation and Migration by Angiotensin II via the Inhibition of ERK1/2 and JNK Signaling Pathways.
Other Titles: Exendin-4はERK1/2とJNKの阻害を介してアンギオテンシンⅡによる血管平滑筋細胞の増殖と遊走を抑制する
Authors: Nagayama, Kosuke
Kyotani, Yoji
Zhao, Jing
Ito, Satoyasu
Ozawa, Kentaro
Bolstad, Francesco A.
Yoshizumi, Masanori
Issue Date: 17-Sep-2015
Publisher: Public Library of Science
Citation: PloS one Vol.10 No.9 p.e0137960(2015 Sep 17)
Abstract: Angiotensin II (Ang II) is a main pathophysiological culprit peptide for hypertension and atherosclerosis by causing vascular smooth muscle cell (VSMC) proliferation and migration. Exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, is currently used for the treatment of type-2 diabetes, and is believed to have beneficial effects for cardiovascular diseases. However, the vascular protective mechanisms of GLP-1 receptor agonists remain largely unexplained. In the present study, we examined the effect of exendin-4 on Ang II-induced proliferation and migration of cultured rat aortic smooth muscle cells (RASMC). The major findings of the present study are as follows: (1) Ang II caused a phenotypic switch of RASMC from contractile type to synthetic proliferative type cells; (2) Ang II caused concentration-dependent RASMC proliferation, which was significantly inhibited by the pretreatment with exendin-4; (3) Ang II caused concentration-dependent RASMC migration, which was effectively inhibited by the pretreatment with exendin-4; (4) exendin-4 inhibited Ang II-induced phosphorylation of ERK1/2 and JNK in a pre-incubation time-dependent manner; and (5) U0126 (an ERK1/2 kinase inhibitor) and SP600125 (a JNK inhibitor) also inhibited both RASMC proliferation and migration induced by Ang II stimulation. These results suggest that exendin-4 prevented Ang II-induced VSMC proliferation and migration through the inhibition of ERK1/2 and JNK phosphorylation caused by Ang II stimulation. This indicates that GLP-1 receptor agonists should be considered for use in the treatment of cardiovascular diseases in addition to their current use in the treatment of diabetes mellitus.
Description: 博士(医学)・甲第648号・平成28年3月15日
Copyright: © 2015 Nagayama et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
URI: http://hdl.handle.net/10564/3185
ISSN: 19326203
Academic Degrees and number: 24601A648
Degree-granting date: 2016-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2015年度

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