J20619 inhibits PDGF‐BB‐stimulated vascular smooth muscle cell proliferation and migration (1065.2)
Lian‐Hua Fang, Jing Guo, Li Li, Yujie Wu, Yu Yan, Xiao‐na Xu, Shoubao Wang, Tianyi Yuan, Guanhua Du
Abstract
Lian‐Hua Fang, Jing Guo, Li Li, Yujie Wu, Yu Yan, Xiao‐na Xu, Shoubao Wang, Tianyi Yuan, Guanhua Du
Abstract
J20619 is a natural pigment isolated from the heartwood of Traditional Chinese Medicine . J20619 has been reported to exhibit various biological activities including anti‐platelet aggregation, anti‐inflammation, and vasorelaxation, etc. However, the effects of J20619 on vascular smooth muscle cell (VSMC) remain unexplored. The present study investigated the effects of J20619 on platelet‐derived growth factor (PDGF)‐BB induced VSMC proliferation and migration and its possible mechanisms. VSMC proliferation and migration were measured by Crystal Violet Staining, wound‐healing and Boyden chamber assays, respectively. Cell cycle was analyzed by flow cytometry. Enzymatic action of matrix metalloproteinase‐9 (MMP‐9) was carried out by gelatin zymography. These study demonstrated that pretreatment with J20619 dose‐dependently inhibited PDGF‐BB stimulated VSMC proliferation and migration, which were associated with cell‐cycle arrest at G0/G1 phase, reduction in the adhesion molecule expression and MMP‐9 activation in VSMCs. Furthermore, the increase in PDGF‐Rβ, Src, ERK1/2 and Akt phosphorylation induced by PDGF‐BB were suppressed by J20619. These findings indicate that J20619 inhibits PDGF‐BB induced VSMC proliferation and migration, and the inhibitory effects may be associated with the blockade of PDGF‐Rβ‐ERK1/2 and Akt signaling pathways. In conclusion, the present study suggests that J20619 may be useful as an anti‐proliferative agent for the treatment of vascular diseases.
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J20619 is a natural pigment isolated from the heartwood of Traditional Chinese Medicine . J20619 has been reported to exhibit various biological activities including anti‐platelet aggregation, anti‐inflammation, and vasorelaxation, etc. However, the effects of J20619 on vascular smooth muscle cell (VSMC) remain unexplored. The present study investigated the effects of J20619 on platelet‐derived growth factor (PDGF)‐BB induced VSMC proliferation and migration and its possible mechanisms. VSMC proliferation and migration were measured by Crystal Violet Staining, wound‐healing and Boyden chamber assays, respectively. Cell cycle was analyzed by flow cytometry. Enzymatic action of matrix metalloproteinase‐9 (MMP‐9) was carried out by gelatin zymography. These study demonstrated that pretreatment with J20619 dose‐dependently inhibited PDGF‐BB stimulated VSMC proliferation and migration, which were associated with cell‐cycle arrest at G0/G1 phase, reduction in the adhesion molecule expression and MMP‐9 activation in VSMCs. Furthermore, the increase in PDGF‐Rβ, Src, ERK1/2 and Akt phosphorylation induced by PDGF‐BB were suppressed by J20619. These findings indicate that J20619 inhibits PDGF‐BB induced VSMC proliferation and migration, and the inhibitory effects may be associated with the blockade of PDGF‐Rβ‐ERK1/2 and Akt signaling pathways. In conclusion, the present study suggests that J20619 may be useful as an anti‐proliferative agent for the treatment of vascular diseases.
Key concepts: Platelet-derived growth factor receptor, Vascular smooth muscle, Cell growth, Cell biology, Protein kinase B, Platelet-derived growth factor, Matrix metalloproteinase, Chemistry