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タイトル別表記
血管平滑筋細胞石灰化シグナルにおけるRhoキナーゼ−サイクロフィリンA経路の関与
著者
津田, 達也 徳島大学大学院医科学教育部(医学専攻)
Oogoshi, Mizuho Tokushima University
堀ノ内, 裕也 Tokushima University
キーワード
Arterial calcification
Cyclophilin A
Rho-associated protein kinase
Vascular smooth muscle cell
Atherosclerosis
資料タイプ
学位論文
抄録
Arterial calcification, a risk factor of cardiovascular events, develops with differentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. Cyclophilin A (CypA) is a peptidyl-prolyl isomerase involved in cardiovascular diseases such as atherosclerosis and aortic aneurysms, and rho-associated protein kinase (ROCK) is involved in the pathogenesis of vascular calcification. CypA is secreted in a ROCK activity-dependent manner and works as a mitogen via autocrine or paracrine mechanisms in VSMCs. We examined the involvement of the ROCK-CypA axis in VSMC calcification induced by inorganic phosphate (Pi), a potent cell mineralization initiator. We found that Pi stimulated ROCK activity, CypA secretion, extracellular signal-regulated protein kinase (ERK) 1/2 phosphorylation, and runt-related transcription factor 2 expression, resulting in calcium accumulation in rat aortic smooth muscle cells (RASMCs). The ROCK inhibitor Y-27632 significantly suppressed Pi-induced CypA secretion, ERK1/2 phosphorylation, and calcium accumulation. Recombinant CypA was found to be associated with increased calcium accumulation in RASMCs. Based on these results, we suggest that autocrine CypA is mediated by ROCK activity and is involved in Pi-induced ERK1/2 phosphorylation following calcification signaling in RASMCs.
掲載誌名
Journal of Pharmacological Sciences
ISSN
13478613
出版者
Japanese Pharmacological Society|Elsevier
142
3
開始ページ
109
終了ページ
115
発行日
2019-12-16
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Tatsuya Tsudaの学位論文として提出され,学位審査・授与の対象となっている。
権利情報
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3572号
学位記番号
甲医第1520号
学位授与年月日
2022-02-24
学位名
博士(医学)
学位授与機関
徳島大学
部局
病院
医学系