Ischemia-induced Netrin-4 promotes neovascularization through endothelial progenitor cell activation via Unc-5 Netrin receptor B

Cited 4 time in scopus
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Title
Ischemia-induced Netrin-4 promotes neovascularization through endothelial progenitor cell activation via Unc-5 Netrin receptor B
Author(s)
Na Geum Lee; I C Jeung; S C Heo; Jinhoi Song; Wooil Kim; Byungtae Hwang; Min-Gi Kwon; Yeon-Gu KimJangwook LeeJong Gil Park; Min Gyeong Shin; Young Lai ChoMi Young SonKwang-Hee Bae; Sang Hyun Lee; J H Kim; Jeong Ki Min
Bibliographic Citation
FASEB Journal, vol. 34, no. 1, pp. 1231-1246
Publication Year
2020
Abstract
Endothelial progenitor cells (EPCs) promote neovascularization and tissue repair by migrating to vascular injury sites; therefore, factors that enhance EPC homing to damaged tissues are of interest. Here, we provide evidence of the prominent role of the Netrin-4 (NTN4)-Unc-5 Netrin receptor B (UNC5B) axis in EPC-specific promotion of ischemic neovascularization. Our results showed that NTN4 promoted the proliferation, chemotactic migration, and paracrine effects of small EPCs (SEPCs) and significantly increased the incorporation of large EPCs (LEPCs) into tubule networks. Additionally, NTN4 prominently augmented neovascularization in mice with hindlimb ischemia by increasing the homing of exogenously transplanted EPCs to the ischemic limb and incorporating EPCs into vessels. Moreover, silencing of UNC5B, an NTN4 receptor, abrogated the NTN4-induced cellular activities of SEPCs in vitro and blood-flow recovery and neovascularization in vivo in ischemic muscle by reducing EPC homing and incorporation. These findings suggest NTN4 as an EPC-based therapy for treating angiogenesis-dependent diseases.
Keyword
EPCbased therapyNetrin4angiogenesisdependent diseasesendothelial progenitor cellsneovascularization
ISSN
0892-6638
Publisher
Wiley
DOI
http://dx.doi.org/10.1096/fj.201900866RR
Type
Article
Appears in Collections:
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
Division of Biomedical Research > Metabolic Regulation Research Center > 1. Journal Articles
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
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