期刊
CELLULAR AND MOLECULAR NEUROBIOLOGY
卷 33, 期 6, 页码 789-801出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10571-013-9946-3
关键词
Blood-Nerve barrier; Endoneurial endothelial cell; Growth factor receptors; Mitogen; Vascular endothelial growth factor
资金
- National Institutes of Health [R21 NS073702, R21 NS078226, R01 NS075212, P30 AI27767]
Several mitogens such as vascular endothelial growth factor (VEGF) have been implicated in mammalian vascular proliferation and repair. However, the molecular mediators of human blood-nerve barrier (BNB) development and specialization are unknown. Primary human endoneurial endothelial cells (pHEndECs) were expanded in vitro and specific mitogen receptors detected by western blot. pHEndECs were cultured with basal medium containing different mitogen concentrations with or without heparin. Non-radioactive cell proliferation, Matrigel((TM))-induced angiogenesis and sterile micropipette injury wound healing assays were performed. Proliferation rates, number and total length of induced microvessels, and rate of endothelial cell monolayer wound healing were determined and compared to basal conditions. VEGF-A(165) in the presence of heparin, was the most potent inducer of pHEndEC proliferation, angiogenesis, and wound healing in vitro. 1.31 nM VEGF-A(165) induced similar to 110 % increase in cell proliferation relative to basal conditions (similar to 51 % without heparin). 2.62 pM VEGF-A(165) induced a three-fold increase in mean number of microvessels and 3.9-fold increase in total capillary length/field relative to basal conditions. In addition, 0.26 nM VEGF-A(165) induced similar to y similar to 1.3-fold increased average rate of endothelial wound healing 4-18 h after endothelial monolayer injury, mediated by increased cell migration. VEGF-A(165) was the only mitogen capable of complete wound closure, occurring within 30 h following injury via increased cell proliferation. This study demonstrates that VEGF-A(165), in the presence of heparin, is a potent inducer of pHEndEC proliferation, angiogenesis, and wound healing in vitro. VEGF-A(165) may be an important mitogen necessary for human BNB development and recovery in response to peripheral nerve injury.
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