BMP-2 induces angiogenesis by provoking integrin α6 expression in human endothelial progenitor cells
| Autor: | Po-Hsun Chou, Yu-Wei Lai, Jen-Kun Cheng, Guo-Shou Wang, Juei-Yu Yen, Min-Huan Wu, Shih-Chia Liu, Li-Yu Wang, Ching-Hu Chung, Shih-Wei Wang, Yih-Jer Wu, Yung-Chang Lu, Hung-I Yeh, Wei-Cheng Chen |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway animal structures Angiogenesis Bone Morphogenetic Protein 2 Gene Expression Neovascularization Physiologic Integrin alpha6 Biochemistry Neovascularization Mice 03 medical and health sciences Cell Movement medicine Animals Humans Progenitor cell Protein kinase B PI3K/AKT/mTOR pathway Endothelial Progenitor Cells Pharmacology Tube formation Dose-Response Relationship Drug Chemistry Cell migration Cell biology Mice Inbred C57BL 030104 developmental biology embryonic structures Leukocytes Mononuclear cardiovascular system medicine.symptom |
| Zdroj: | Biochemical Pharmacology. 150:256-266 |
| ISSN: | 0006-2952 |
| Popis: | Bone morphogenetic protein-2 (BMP-2) is a multifunctional cytokine, capable of governing several cellular functions, including proliferation, motility, differentiation, and angiogenesis. Circulating endothelial progenitor cells (EPCs) have been shown to facilitate tissue repair, postnatal neovascularization, and tumor associated angiogenesis. Nevertheless, the impact of BMP-2 on angiogenesis of human EPCs has largely remained a mystery. In this study, we found 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 α6 by siRNA transfection obviously attenuated BMP-2-indueced tube formation of EPCs. These results 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect