TY - JOUR
T1 - Rho-associated protein kinase and cyclophilin a are involved in inorganic phosphate-induced calcification signaling in vascular smooth muscle cells
AU - Tsuda, Tatsuya
AU - Imanishi, Masaki
AU - Oogoshi, Mizuho
AU - Goda, Mitsuhiro
AU - Kihira, Yoshitaka
AU - Horinouchi, Yuya
AU - Zamami, Yoshito
AU - Ishizawa, Keisuke
AU - Ikeda, Yasumasa
AU - Hashimoto, Ichiro
AU - Tamaki, Toshiaki
AU - Izawa-Ishizawa, Yuki
N1 - Funding Information:
This work was supported by grants from JSPS KAKENHI Grant Number JP26860172, JP16K08549 (Y.I.-I.), and the Naito Foundation (Y.I.-I.).
Funding Information:
This work was supported by grants from JSPS KAKENHI Grant Number JP26860172 , JP16K08549 (Y.I.-I.), and the Naito Foundation (Y.I.-I.).
Publisher Copyright:
© 2019 The Authors
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
KW - Arterial calcification
KW - Atherosclerosis
KW - Cyclophilin A
KW - Rho-associated protein kinase
KW - Vascular smooth muscle cell
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U2 - 10.1016/j.jphs.2019.12.005
DO - 10.1016/j.jphs.2019.12.005
M3 - Article
C2 - 31882204
AN - SCOPUS:85076980542
SN - 1347-8613
VL - 142
SP - 109
EP - 115
JO - Journal of Pharmacological Sciences
JF - Journal of Pharmacological Sciences
IS - 3
ER -
