alpha-Iso-Cubebene Inhibits PDGF-Induced Vascular Smooth Muscle CellProliferation by Suppressing Osteopontin Expression

Collection with item attached
2017
Item details URL
http://open-repository.kisti.re.kr/cube/handle/open_repository/474440.do
DOI
10.1371/journal.pone.0170699
Title
alpha-Iso-Cubebene Inhibits PDGF-Induced Vascular Smooth Muscle CellProliferation by Suppressing Osteopontin Expression
Description
This research was supported by Basic Science Research Program throughthe National Research Foundation of Korea (NRF) funded by the Ministryof Science, ICT and future Planning (NRF-2013R1A2A2A01067921 &NRF-2016R1A2B2011509). This work was also supported by the MedicalResearch Center (MRC) Program through the NRF grant funded by the Koreagovernment (MSIP) (NRF-2015R1A5A2009656).
abstract
alpha-Iso-cubebene (ICB) is a dibenzocyclooctadiene lignin contained in Schisandra chinensis (SC), a well-known medicinal herb that ameliorates cardiovascular symptoms. Thus, we examined the effect of ICB on vascular smooth muscle cell (VSMC) proliferation, a key feature of diverse vascular diseases. When VSMCs primary cultured from rat thoracic aorta were stimulated with PDGF (1-10 ng/ml), cell proliferation and osteopontin (OPN) expression were concomitantly up-regulated, but these effects were attenuated when cells were treated with MPIIIB10, a neutralizing monoclonal antibody for OPN. In aortic tissues exposed to PDGF, sprouting VSMC numbers increased, which was attenuated in tissues from OPN-deficient mice. Furthermore, VSMC proliferation and OPN expression induced by PDGF were attenuated dose-dependently by ICB (10 or 30 mu g/ml). Reporter assays conducted using OPN promoter-luciferase constructs showed that the promoter region 538-234 bp of the transcription start site was responsible for transcriptional activity enhancement by PDGF, which was significantly inhibited by ICB. Putative binding sites for AP-1 and C/EBP beta in the indicated promoter region were suggested by TF Search, and increased binding of AP-1 and C/EBPa in PDGF-treated VSMCs was demonstrated using a ChIP assay. The increased bindings of AP-1 and C/EBP into OPN promoter were attenuated by ICB. Moreover, the PDGF-induced expression of OPN was markedly attenuated in VSMCs transfected with siRNA for AP-1 and C/EBP beta. These results indicate that ICB inhibit VSMC proliferation by inhibiting the AP-1 and C/EBP beta signaling pathways and thus downregulating OPN expression.
provenance
Made available in Cube on 2018-09-28T10:46:07Z (GMT). No. of bitstreams: 0
language
English
author
Jang, Min A.
Lee, Seung Jin
Baek, Seung Eun
Park, So Youn
Choi, Young Whan
Kim, Chi Dae
accessioned
2018-09-28T10:46:07Z
available
2018-09-28T10:46:07Z
issued
2017
citation
PLOS ONE(12): 1
issn
1932-6203
uri
http://open-repository.kisti.re.kr/cube/handle/open_repository/474440.do
Funder
교육부
Funding Program
BK21플러스사업(0.5)
Project ID
1345274072
Jurisdiction
Rep.of Korea
Project Name
PNU BK21 Plus Biomedical Science Education Center
rights
openAccess
type
article


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