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Heat shock protein 90 inhibitor AUY922 attenuates platelet-derived growth factor-BB-induced migration and proliferation of vascular smooth muscle cells

Title
Heat shock protein 90 inhibitor AUY922 attenuates platelet-derived growth factor-BB-induced migration and proliferation of vascular smooth muscle cells
Authors
Kim, JisuLee, Kang PaKim, Born SahnLee, Sang JuMoon, Byung SeokBaek, Suji
Ewha Authors
김범산문병석
SCOPUS Author ID
김범산scopus
Issue Date
2020
Journal Title
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
ISSN
1226-4512JCR Link

2093-3827JCR Link
Citation
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY vol. 24, no. 3, pp. 241 - 248
Keywords
AtherosclerosisAUY922Heat shock protein 90Platelet-derived growth factorVascular disease
Publisher
KOREAN JOURNAL OF PHYSIOLOGY &

PHARMACOLOGY
Indexed
SCIE; SCOPUS; KCI WOS
Document Type
Article
Abstract
Luminespib (AUY922), a heat shock proteins 90 inhibitor, has anti-neoplastic and antitumor effects. However, it is not clear whether AUY922 affects events in vascular diseases. We investigated the effects of AUY922 on the platelet-derived growth factor (PDGF)-BB-stimulated proliferation and migration of vascular smooth muscle cells (VSMC). VSMC viability was detected using the XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reagent. To detect the attenuating effects of AUY922 on PDGF-BB-induced VSMCs migration in vitro, we performed the Boyden chamber and scratch wound healing assays. To identify AUY922-mediated changes in the signaling pathway, the phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) 1/2 was analyzed by immunoblotting. The inhibitory effects of AUY922 on migration and proliferation ex vivo were tested using an aortic ring assay. AUY922 was not cytotoxic at concentrations up to 5 nM. PDGF-BB-induced VSMC proliferation, migration, and sprout outgrowth were significantly decreased by AUY922 in a dose-dependent manner. AUY922 significantly reduced the PDGF-BB-stimulated phosphorylation of Akt and ERK1/2. Furthermore, PD98059 (a selective ERK1/2 inhibitor) and LY294002 (a selective Akt inhibitor) decreased VSMC migration and proliferation by inhibiting phosphorylation of Akt and ERK1/2. Greater attenuation of PDGF-BB-induced cell viability and migration was observed upon treatment with PD98059 or LY294002 in combination with AUY922. AUY922 showed anti-proliferation and anti-migration effects towards PDGF-BB-induced VSMCs by regulating the phosphorylation of ERK1/2 and Akt. Thus, AUY922 is a candidate for the treatment of atherosclerosis and restenosis.
DOI
10.4196/kjpp.2020.24.3.241
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의과대학 > 의학과 > Journal papers
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