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http://hdl.handle.net/10564/3185
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タイトル: | Exendin-4 Prevents Vascular Smooth Muscle Cell Proliferation and Migration by Angiotensin II via the Inhibition of ERK1/2 and JNK Signaling Pathways. |
その他のタイトル: | 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 |
著者: | Nagayama, Kosuke Kyotani, Yoji Zhao, Jing Ito, Satoyasu Ozawa, Kentaro![](/dspace/image/metalink/link_ja.gif) Bolstad, Francesco A. Yoshizumi, Masanori![](/dspace/image/metalink/link_ja.gif) |
発行日: | 2015年9月17日 |
出版者: | Public Library of Science |
引用: | PloS one Vol.10 No.9 Article No.e0137960 (2015 Sep 17) |
抄録: | 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. |
内容記述: | 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 |
DOI: | http://dx.doi.org/10.1371/journal.pone.0137960 |
学位授与番号: | 24601A648 |
学位授与年月日: | 2016-03-15 |
学位名: | 博士(医学) |
学位授与機関: | 奈良県立医科大学 |
出現コレクション: | 2015年度
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