Alternative TitleExendin-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
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
DOIinfo:doi/10.1371/journal.pone.0137960
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2016-05-01T16:38:40+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション