Ischemia-induced Netrin-4 promotes neovascularization through endothelial progenitor cell activation via Unc-5 Netrin receptor B
| Autor: | Na Geum Lee, Byungtae Hwang, Jeong-Ki Min, Young-Lai Cho, Soon Chul Heo, Yeon-Gu Kim, Min‐Gyeong Shin, Kwang-Hee Bae, Mi-Young Son, Min-Gi Kwon, Jong-Gil Park, Wooil Kim, Sang-Hyun Lee, Jae Ho Kim, Jinhoi Song, Jangwook Lee, In Cheul Jeung |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Ischemia Mice Nude Biochemistry Endothelial progenitor cell Neovascularization 03 medical and health sciences Paracrine signalling Mice 0302 clinical medicine Netrin Genetics medicine Animals Humans Gene Silencing Progenitor cell Receptor Muscle Skeletal Molecular Biology Endothelial Progenitor Cells Mice Inbred BALB C Neovascularization Pathologic Chemistry medicine.disease Cell biology Hindlimb 030104 developmental biology embryonic structures cardiovascular system Heterografts Netrins medicine.symptom Netrin Receptors 030217 neurology & neurosurgery circulatory and respiratory physiology Biotechnology Homing (hematopoietic) |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 34(1) |
| ISSN: | 1530-6860 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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