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BMP9 Induces Cord Blood-Derived Endothelial Progenitor Cell Differentiation and Ischemic Neovascularization via ALK1
- BMP9 Induces Cord Blood-Derived Endothelial Progenitor Cell Differentiation and Ischemic Neovascularization via ALK1
- Kim, J[Kim, Jihye]; Kim, M[Kim, Minhyung]; Jeong, Y[Jeong, Yoonjeong]; Lee, WB[Lee, Wook-bin]; Park, H[Park, Hyojin]; Kwon, JY[Kwon, Ja-Young]; Kim, YM[Kim, Young-Myeong]; Hwang, D[Hwang, Daehee]; Kwon, YG[Kwon, Young-Guen]
- DGIST Authors
- Hwang, D[Hwang, Daehee]
- Issue Date
- Arteriosclerosis, Thrombosis, and Vascular Biology, 35(9), 2020-2031
- Article Type
- Activin Receptor 1; Activin Receptor Like Kinase 1; Activin Receptors; Activin Receptors, Type I; Acvrl1 Protein, Mouse; Angiogenesis; Animal; Animal Experiment; Animal Model; Animals; Biosynthesis; Blood; Bone Morphogenetic Protein 9; Cell Adhesion; Cell Culture; Cell Density; Cell Differentiation; Cell Maturation; Cells, Cultured; Controlled Study; Cytology; Disease Model; Disease Models, Animal; Endothelial Cells; Endothelial Progenitor Cell; Endothelial Progenitor Cells; Extracellular Matrix; Fetal Blood; Fetus Blood; Flow Cytometry; Gdf2 Protein, Mouse; Gene Expression; Gene Expression Regulation; Genetics; Growth Differentiation Factor 2; Human; Human Cell; Humans; In Vitro Study; Ischemia; Limb Ischemia; Male; Metabolism; Mice; Mice, Nude; Mouse; Neo-Vascularization (Pathology); Neo-Vascularization, Pathologic; Non-Human; Nude Mouse; Pathology; Phenotype; Priority Journal; Protein Expression; Protein Phosphorylation; Reverse Transcriptase-Polymerase Chain Reaction; RNA; Signal Transduction; Smad1 Protein; Smad5 Protein; Smad8 Protein; Transforming Growth Factor Beta; Umbilical Cord Blood
- Objective - Modulating endothelial progenitor cells (EPCs) is essential for therapeutic angiogenesis, and thus various clinical trials involving EPCs are ongoing. However, the identification of environmental conditions and development of optimal methods are required to accelerate EPC-driven vasculogenesis. Approach and Results - We evaluated gene expression profiles of cord blood-derived EPCs and endothelial cells to identify the key factors in EPC→endothelial cell differentiation and to show that transforming growth factor-β family members contribute to EPC differentiation. The expression levels of activin receptor-like kinase 1 (ALK1) and its high-affinity ligand, bone morphogenetic protein 9 (BMP9) were markedly changed in EPC→endothelial cell differentiation. Interestingly, BMP9 induced EPC→endothelial cell differentiation and EPC incorporation into vessel-like structures by acting on ALK1 expressed on EPCs in vitro. BMP9 also induced neovascularization in mice with hindlimb ischemia by increasing vessel formation and the incorporation of EPCs into vessels. Conversely, neovascularization was impaired when ALK1 signaling was blocked. Furthermore, EPCs exposed to either short- or long-term BMP9 stimulation demonstrated these functions in EPC-mediated neovascularization. Conclusions - Collectively, our results indicated that BMP9/ALK1 augmented vasculogenesis and angiogenesis, and thereby enhanced neovascularization. Thus, we suggest that BMP9/ALK1 may improve the efficacy of EPC-based therapies for treating ischemic diseases. © 2015 American Heart Association, Inc.
- Lippincott Williams and Wilkins
- Related Researcher
Hwang, Dae Hee
Systems Biology and Medicine Lab
Multilayered spatiotemporal networks; Regulatory motifs or pathways; Metabolite-protein networks; Network stochasticity; Proteomics and informatics
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