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α-Iso-Cubebene Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation by Suppressing Osteopontin Expression
α-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. Wh...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5256966/ https://www.ncbi.nlm.nih.gov/pubmed/28114367 http://dx.doi.org/10.1371/journal.pone.0170699 |
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author | Jang, Min A. Lee, Seung Jin Baek, Seung Eun Park, So Youn Choi, Young Whan Kim, Chi Dae |
author_facet | Jang, Min A. Lee, Seung Jin Baek, Seung Eun Park, So Youn Choi, Young Whan Kim, Chi Dae |
author_sort | Jang, Min A. |
collection | PubMed |
description | α-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 μg/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/EBPβ in the indicated promoter region were suggested by TF Search, and increased binding of AP-1 and C/EBPβ in PDGF-treated VSMCs was demonstrated using a ChIP assay. The increased bindings of AP-1 and C/EBPβ 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/EBPβ. These results indicate that ICB inhibit VSMC proliferation by inhibiting the AP-1 and C/EBPβ signaling pathways and thus downregulating OPN expression. |
format | Online Article Text |
id | pubmed-5256966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-52569662017-02-06 α-Iso-Cubebene Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation by Suppressing Osteopontin Expression Jang, Min A. Lee, Seung Jin Baek, Seung Eun Park, So Youn Choi, Young Whan Kim, Chi Dae PLoS One Research Article α-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 μg/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/EBPβ in the indicated promoter region were suggested by TF Search, and increased binding of AP-1 and C/EBPβ in PDGF-treated VSMCs was demonstrated using a ChIP assay. The increased bindings of AP-1 and C/EBPβ 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/EBPβ. These results indicate that ICB inhibit VSMC proliferation by inhibiting the AP-1 and C/EBPβ signaling pathways and thus downregulating OPN expression. Public Library of Science 2017-01-23 /pmc/articles/PMC5256966/ /pubmed/28114367 http://dx.doi.org/10.1371/journal.pone.0170699 Text en © 2017 Jang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Jang, Min A. Lee, Seung Jin Baek, Seung Eun Park, So Youn Choi, Young Whan Kim, Chi Dae α-Iso-Cubebene Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation by Suppressing Osteopontin Expression |
title | α-Iso-Cubebene Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation by Suppressing Osteopontin Expression |
title_full | α-Iso-Cubebene Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation by Suppressing Osteopontin Expression |
title_fullStr | α-Iso-Cubebene Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation by Suppressing Osteopontin Expression |
title_full_unstemmed | α-Iso-Cubebene Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation by Suppressing Osteopontin Expression |
title_short | α-Iso-Cubebene Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation by Suppressing Osteopontin Expression |
title_sort | α-iso-cubebene inhibits pdgf-induced vascular smooth muscle cell proliferation by suppressing osteopontin expression |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5256966/ https://www.ncbi.nlm.nih.gov/pubmed/28114367 http://dx.doi.org/10.1371/journal.pone.0170699 |
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