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2016 ; 37
(5
): 1239-46
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Magnobovatol inhibits smooth muscle cell migration by suppressing PDGF-R?
phosphorylation and inhibiting matrix metalloproteinase-2 expression
#MMPMID27049716
Kang H
; Ahn DH
; Pak JH
; Seo KH
; Baek NI
; Jang SW
Int J Mol Med
2016[May]; 37
(5
): 1239-46
PMID27049716
show ga
The migration of vascular smooth muscle cells (VSMCs) may play a crucial role in
the pathogenesis of vascular diseases, such as atherosclerosis and
post-angioplasty restenosis. Platelet-derived growth factor (PDGF)-BB is a potent
mitogen for VSMCs and plays an important role in the intimal accumulation of
VSMCs. Magnobovatol, a new neolignan from the fruits of Magnolia obovata, has
been shown to have anticancer properties. However, the effects of magnobovatol on
VSMCs are unknown. In the present study, we examined the effects of magnobovatol
on the PDGF?BB?induced migration of mouse and human VSMCs, as well as the
underlying mechanisms. Magnobovatol significantly inhibited the PDGF?BB-induced
migration of mouse and human VSMCs without inducing cell death (as shown by MTT
assay and wound healing assay). Additionally, we demonstrated that magnobovatol
significantly blocked the PDGF?BB-induced phosphorylation of the PDGF receptor
(PDGF-R), Akt and extracellular signal?regulated kinase (ERK)1/2 by inhibiting
the activation of the PDGF?BB signaling pathway. Moreover, in both mouse and
human VSMCs, magnobovatol inhibited PDGF-induced matrix metalloproteinase (MMP)-2
expression at the mRNA and protein level, as well as the proteolytic activity of
MMP-2 (as shown by western blot analysis, RT-PCR, gelatin zymography and ELISA).
In addition, the sprout outgrowth formation of aortic rings induced by PDGF?BB
was inhibited by magnobovatol (as shown by aortic ring assay). Taken together,
our findings indicate that magnobovatol inhibits VSMC migration by decreasing
MMP-2 expression through PDGF-R and the ERK1/2 and Akt pathways. Our data may
improve the understanding of the anti-atherogenic effects of magnobovatol in
VSMCs.