Rho-associated protein kinase and cyclophilin a are involved in inorganic phosphate-induced calcification signaling in vascular smooth muscle cells

• Material Type: 博士論文
• ISSN: 1347-8613
• Title: Rho-associated protein kinase and cyclophilin a are involved in inorganic phosphate-induced calcification signaling in vascular smooth muscle cells
• Volume: 142 3
• Author/Editor: Tsuda, Tatsuya; Imanishi, Masaki; Oogoshi, Mizuho; Goda, Mitsuhiro; Kihira, Yoshitaka; Horinouchi, Yuya; Zamami, Yoshito; Ishizawa, Keisuke; Ikeda, Yasumasa; Hashimoto, Ichiro; Tamaki, Toshiaki; Izawa-Ishizawa, Yuki
• Author Heading: Tsuda, Tatsuya; Imanishi, Masaki; Oogoshi, Mizuho; Goda, Mitsuhiro; Kihira, Yoshitaka; Horinouchi, Yuya; Zamami, Yoshito; Ishizawa, Keisuke; Ikeda, Yasumasa; Hashimoto, Ichiro; Tamaki, Toshiaki; Izawa-Ishizawa, Yuki
• Publication, Distribution, etc.: Japanese Pharmacological Society|Elsevier
• Publication Date: 2019-12-16
• Publication Date (W3CDTF): 2019-12-16
• Alternative Title: 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
• Periodical title: Journal of Pharmacological Sciences
• Degree grantor/type: 徳島大学
• Date Granted: 2022-02-24
• Date Granted (W3CDTF): 2022-02-24
• Dissertation Number: 甲第3572号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3572号
• Text Language Code: eng
• Subject Heading: Arterial calcification; Cyclophilin A; Rho-associated protein kinase; Vascular smooth muscle cell; Atherosclerosis
• Target Audience: 一般
• Note (General): 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.
• DOI: info:doi/10.1016/j.jphs.2019.12.005; https://doi.org/info:doi/10.1016/j.jphs.2019.12.005
• Persistent ID (NDL): info:ndljp/pid/12263953; https://dl.ndl.go.jp/pid/12263953
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• Date Accepted (W3CDTF): 2022-05-09T11:57:37+09:00
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/115530
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