Ginkgolide B promotes proliferation and functional activities of bone marrow-derived endothelial progenitor cells: involvement of Akt/eNOS and MAPK/p38 signaling pathways

• Published in: European cells & materials Vol. 21; pp. 459 - 469
• Main Authors: Tang, Yubo, Huang, Baoding, Sun, Laibao, Peng, Xinsheng, Chen, Xiao, Zou, Xuenong
• Format: Journal Article
• Language: English
• Published: Switzerland Forum Multimedia Publishing LLC 28-05-2011
• Subjects: Adult; Adult Stem Cells - cytology; Adult Stem Cells - drug effects; Adult Stem Cells - metabolism; Aged; Akt; angiogenesis; Antigens, CD - genetics; Antigens, CD - metabolism; Apoptosis - drug effects; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Cadherins - genetics; Cadherins - metabolism; Cell Adhesion - drug effects; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Shape; Cell Survival - drug effects; Endothelial Cells - cytology; Endothelial Cells - drug effects; Endothelial Cells - metabolism; endothelial nitric oxide synthase (eNOS); Endothelial progenitor cells; Ginkgolide B; Ginkgolides - pharmacology; Humans; Hydrogen Peroxide - pharmacology; Lactones - pharmacology; MAP Kinase Signaling System; Middle Aged; Necrosis; Neovascularization, Physiologic - drug effects; Nitric Oxide Synthase Type III - genetics; Nitric Oxide Synthase Type III - metabolism; p38; p38 Mitogen-Activated Protein Kinases - physiology; Phosphorylation; proliferation; Proto-Oncogene Proteins c-akt - metabolism; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-2 - metabolism
• ISSN: 1473-2262; 1473-2262
• DOI: 10.22203/eCM.v021a34

Bone marrow-derived, circulating endothelial progenitor cells (EPCs) contribute to neovascularization in various diseases, and represent a very interesting alternative cell source for enhancing vasculogenesis in regenerative medicine. In this study, we investigated the effects of Ginkgolide B (GB) on proliferation and differentiation of EPCs, and the involved signaling pathway in vitro. EPC proliferation, migration, adhesion and angiogenesis activities were assessed with the WST-8 assay, Transwell chamber assay, cell counting and angiogenesis kit, respectively. Apoptosis was detected with annexin V and propidium iodide staining. The protein expression of angiogenesis-related makers was detected by Western blot, and related gene expression was determined by real-time polymerase chain reaction (RT-PCR). The results showed that GB promoted the proliferation and endothelial gene expression, and markedly enhanced vascular endothelial growth factor-induced migration response and the capability to incorporate into the vascular networks in EPCs. GB protected EPCs from H2O2-induced cell death. GB induced the phosphorylation of eNOS, Akt and p38, which in turn promoted cell proliferation and function. In conclusion, the present study demonstrates that GB, at a near medical applied dose, increases the number and functional activities of EPCs with involvement of Akt/endothelial nitric oxide synthase and mitogen-activated protein kinase (MAPK)/p38 signal pathways. These findings raise the intriguing possibility that GB may play an important role in the protection and revascularization of blood vessels.