title: Magnobovatol inhibits smooth muscle cell migration by suppressing PDGF-Rβ phosphorylation and inhibiting matrix metalloproteinase-2 expression.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736, Rebublic of Korea.
authors.forename: Hyreen
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Medicine, University of Ulsan College of Medicine, Seoul 138-736, Rebublic of Korea.
authors.forename: Dong Hyeon
authors.initials: DH
authors.lastname: Ahn
authors.affiliation: Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 138-736, Rebublic of Korea.
authors.forename: Jhang Ho
authors.initials: JH
authors.lastname: Pak
authors.affiliation: Department of Oriental Medicine Biotechnology, Kyung Hee University, Yongin, Gyeonggi 446-701, Rebublic of Korea.
authors.forename: Kyeong-Hwa
authors.initials: KH
authors.lastname: Seo
authors.affiliation: Department of Oriental Medicine Biotechnology, Kyung Hee University, Yongin, Gyeonggi 446-701, Rebublic of Korea.
authors.forename: Nam-In
authors.initials: NI
authors.lastname: Baek
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736, Rebublic of Korea.
authors.forename: Sung-Wuk
authors.initials: SW
authors.lastname: Jang
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001011:Aorta; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D010766:Phosphorylation; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D017705:Lignans; C587653:magnobovatol; D020797:Receptor, Platelet-Derived Growth Factor beta; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2