- 期刊
- OpenAccess
【論文摘要】BMP-2 Induces Angiogenesis by Provoking Integrin α6 Expression in Human Endothelial Progenitor Cells
摘要
Background/Synopsis: Bone morphogenetic proteins-2 (BMP-2) is a multifunctional cytokine, capable of governing several cellular functions, including proliferation, motility, differentiation, and angiogenesis. Circulating endothelial progenitor cells (EPCs) are a population of cells in the circulation and carry out angiogenesis and vascular remodeling in maintaining vessel integrity and facilitating tissue repair. Compelling studies support the role of EPCs in tissue repair and regenerative medicine. Understanding of EPCs function improves insight into the potential utility for therapeutic vascular regeneration. Objectives/Purpose: Plentiful studies have confirmed that BMP-2 is an important angiogenic modulator in angiogenesis-related diseases. However, the regulation of BMP-2 on integrin α6 in EPCs is mostly unknown. The angiogenic effect and mechanism of BMP-2 on EPCs has not been well investigated. In this study, we investigated the relationship of BMP-2 with integrin α6 and angiogenesis, and further elucidated its mechanism of action in human EPCs. Methods/Results: Our results showed that BMP-2 promoted cell migration and tube formation of EPCs in a concentration-dependent manner, indicating BMP-2 induced in vitro angiogenesis in human EPCs. Furthermore, BMP-2 significantly increased microvessel formation in Matrigel plug assay, and BMP-2 antagonist noggin prevented BMP-2-induced in vivo angiogenesis. Mechanistic investigations showed BMP-2 profoundly induced the expression of Id-1 and integrin α6 as well as EPCs angiogenesis by activating PI3K/Akt and MEK/Erk signaling pathways. Moreover, knockdown of Id-1 and integrin a6 by siRNA transfection obviously attenuated BMP-2-indueced tube formation of EPCs. Conclusion: These findings suggest that BMP-2 promotes angiogenesis in human EPCs through the activation of PI3K/Akt, MEK/ERK, and Id-1/integrin α6 signaling cascades. This is the first demonstration that BMP-2 exhibits the angiogenesis property on human EPCs. BMP-2 might serve as the potential therapeutic target for treatment of angiogenesis-related diseases.