Exendin-4 Prevents Vascular Smooth Muscle Cell Proliferation and Migration by Angiotensin II via the Inhibition of ERK1/2 and JNK Signaling Pathways.

• Material Type: 博士論文
• Title: Exendin-4 Prevents Vascular Smooth Muscle Cell Proliferation and Migration by Angiotensin II via the Inhibition of ERK1/2 and JNK Signaling Pathways.
• Author/Editor: Nagayama, Kosuke; Kyotani, Yoji; Zhao, Jing; Ito, Satoyasu; Ozawa, Kentaro; Bolstad, Francesco A.; Yoshizumi, Masanori
• Author Heading: Nagayama, Kosuke; Kyotani, Yoji; Zhao, Jing; Ito, Satoyasu; Ozawa, Kentaro; Bolstad, Francesco A.; Yoshizumi, Masanori
• Publication, Distribution, etc.: Public Library of Science
• Publication Date: 2015-09-17
• Publication Date (W3CDTF): 2015-09-17
• Alternative Title: 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
• Periodical title: PloS one
• No. or year of volume/issue: 10 9
• Volume: 10
• Issue: 9
• Pages: Article No.e0137960-
• ISSN (Periodical Title): ISSN : 1932-6203
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2016-03-15
• Dissertation Number: 甲第648号
• Degree Type: 博士（医学）
• Text Language Code: und
• Target Audience: 一般
• Note (General): type:Thesis; 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.; 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.; identifier:PloS one Vol.10 No.9 Article No.e0137960 (2015 Sep 17); identifier:19326203; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3185; identifier:PloS one, 10(9): Article No.e0137960
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1371/journal.pone.0137960
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3185/1/01_%e7%94%b2648%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3185/3/03_%e7%94%b2648%e6%9c%ac%e6%96%87.pdf fulltext