0 174

Cited 15 times in

BMP9 Induces Cord Blood-Derived Endothelial Progenitor Cell Differentiation and Ischemic Neovascularization via ALK1

 Jihye Kim  ;  Minhyung Kim  ;  Yoonjeong Jeong  ;  Wook-bin Lee  ;  Hyojin Park  ;  Ja-Young Kwon  ;  Young-Myeong Kim  ;  Daehee Hwang  ;  Young-Guen Kwon 
 Arteriosclerosis Thromobosis and Vascular Biology, Vol.35(9) : 2020-2031, 2015 
Journal Title
 Arteriosclerosis Thromobosis and Vascular Biology 
Issue Date
Activin Receptors, Type I/biosynthesis ; Activin Receptors, Type I/genetics* ; Animals ; Cell Differentiation ; Cells, Cultured ; Disease Models, Animal ; Endothelial Progenitor Cells/metabolism ; Endothelial Progenitor Cells/pathology* ; Fetal Blood/cytology* ; Flow Cytometry ; Gene Expression Regulation* ; Growth Differentiation Factor 2/biosynthesis ; Growth Differentiation Factor 2/genetics* ; Humans ; Ischemia/genetics* ; Ischemia/metabolism ; Ischemia/pathology ; Male ; Mice ; Mice, Nude ; Neovascularization, Pathologic/blood ; Neovascularization, Pathologic/genetics* ; Neovascularization, Pathologic/pathology ; RNA/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction
activin receptors ; endothelial cells ; endothelial progenitor cells ; growth differentiation factor 2 ; ischemia ; neovascularization, pathologic
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.
Full Text
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
Kwon, Ja Young(권자영) ORCID logo https://orcid.org/0000-0003-3009-6325
사서에게 알리기


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.