Clitocybin B inhibits rat aortic smooth muscle cell proliferation through suppressing PDGF-Rβ phosphorylation

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Title
Clitocybin B inhibits rat aortic smooth muscle cell proliferation through suppressing PDGF-Rβ phosphorylation
Author(s)
K D Yoo; E S Park; Y Lim; S I Kang; S H Yoo; H H Won; H P Lee; Y H Kim; Ick-Dong Yoo; H S Yoo; J T Hong; Y P Yun
Bibliographic Citation
Vascular Pharmacology, vol. 56, no. 1, pp. 91-97
Publication Year
2012
Abstract
The increased proliferation of vascular smooth muscle cells (VSMCs) in the arterial wall is a critical pathogenic factor for vascular diseases such as atherosclerosis and restenosis after angioplasty. Clitocybin B was reported to have either a potent free radical scavenging effect or effects that were isolated from the culture broth of mushroom Clitocybe aurantiaca. The present study was designed to investigate the effects of clitocybin B on VSMC proliferation and its possible molecular mechanism. Clitocybin B significantly inhibited the proliferation and the DNA synthesis of PDGF-BB-stimulated VSMCs in a concentration-dependent manner. In agreement with these findings, clitocybin B suppressed the PDGF-BB-induced progression through G0/G1 to S phase of cell cycle. Clitocybin B also down-regulated the expressions of cell cycle-related proteins, including cyclin-dependent kinase (CDK)2, cyclin E, CDK4, cyclin D1, and proliferative cell nuclear antigen in PDGF-BB-stimulated VSMCs. Clitocybin B significantly inhibited the phosphorylation of Akt, extracellular signal-regulated kinase 1/2, and phospholipase C-γ1, in the PDGF-BB signaling pathway. Clitocybin B suppressed the PDGF-Rβ activation in PDGF-BB signaling cascade. These results suggested that the inhibitory effect of clitocybin B on the proliferation of VSMCs may be associated with suppressing PDGF-Rβ phosphorylation. Thus, clitocybin B may be an effective antiproliferative agent for the prevention of atherosclerosis and restenosis.
Keyword
Clitocybin B → ClitocybinPDGF-R → atherosclerosisProliferationVascular smooth muscle cell
ISSN
1537-1891
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.vph.2011.11.004
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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