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ID 115530
Title Alternative
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
Author
Tsuda, Tatsuya Tokushima University
Oogoshi, Mizuho Tokushima University
Horinouchi, Yuya Tokushima University
Keywords
Arterial calcification
Cyclophilin A
Rho-associated protein kinase
Vascular smooth muscle cell
Atherosclerosis
Content Type
Thesis or Dissertation
Description
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.
Journal Title
Journal of Pharmacological Sciences
ISSN
13478613
Publisher
Japanese Pharmacological Society|Elsevier
Volume
142
Issue
3
Start Page
109
End Page
115
Published Date
2019-12-16
Remark
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。
Rights
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3572号
Diploma Number
甲医第1520号
Granted Date
2022-02-24
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
University Hospital
Medical Sciences