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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]
Issued Date
Article Type
Activin Receptor 1Activin Receptor Like Kinase 1Activin ReceptorsActivin Receptors, Type IAcvrl1 Protein, MouseAngiogenesisAnimalAnimal ExperimentAnimal ModelAnimalsBiosynthesisBloodBone Morphogenetic Protein 9Cell AdhesionCell CultureCell DensityCell DifferentiationCell MaturationCells, CulturedControlled StudyCytologyDisease ModelDisease Models, AnimalEndothelial CellsEndothelial Progenitor CellEndothelial Progenitor CellsExtracellular MatrixFetal BloodFetus BloodFlow CytometryGdf2 Protein, MouseGene ExpressionGene Expression RegulationGeneticsGrowth Differentiation Factor 2HumanHuman CellHumansIn Vitro StudyIschemiaLimb IschemiaMaleMetabolismMiceMice, NudeMouseNeo-Vascularization (Pathology)Neo-Vascularization, PathologicNon-HumanNude MousePathologyPhenotypePriority JournalProtein ExpressionProtein PhosphorylationReverse Transcriptase-Polymerase Chain ReactionRNASignal TransductionSmad1 ProteinSmad5 ProteinSmad8 ProteinTransforming Growth Factor BetaUmbilical 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
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Department of New Biology Systems Biology and Medicine Lab 1. Journal Articles


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