RESUMO
Transcriptional mechanisms that drive angiogenesis and organotypic vascular endothelial cell specialization are poorly understood. Here, we show that retinal endothelial sphingosine 1-phosphate receptors (S1PRs), which restrain vascular endothelial growth factor (VEGF)-induced angiogenesis, spatially restrict expression of JunB, a member of the activator protein 1 (AP-1) family of transcription factors (TFs). Mechanistically, VEGF induces JunB expression at the sprouting vascular front while S1PR-dependent vascular endothelial (VE)-cadherin assembly suppresses JunB expression in the nascent vascular network, thus creating a gradient of this TF. Endothelial-specific JunB knockout mice showed diminished expression of neurovascular guidance genes and attenuated retinal vascular network progression. In addition, endothelial S1PR signaling is required for normal expression of ß-catenin-dependent genes such as TCF/LEF1 and ZIC3 TFs, transporters, and junctional proteins. These results show that S1PR signaling restricts JunB function to the expanding vascular front, thus creating an AP-1 gradient and enabling organotypic endothelial cell specialization of the vascular network.
Assuntos
Células Endoteliais/metabolismo , Neovascularização Fisiológica , Vasos Retinianos/metabolismo , Transdução de Sinais , Receptores de Esfingosina-1-Fosfato/metabolismo , Fator de Transcrição AP-1/metabolismo , Animais , Células Cultivadas , Montagem e Desmontagem da Cromatina , Células Endoteliais/citologia , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vasos Retinianos/citologia , Vasos Retinianos/embriologia , Fator de Transcrição AP-1/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
STUDY DESIGN: A case report. OBJECTIVE: We report on the device failure of a polyetherether-ketone expandable cage device with posterior migration of one of its components. SUMMARY OF BACKGROUND DATA: Posterior migration of transforaminal lumbar interbody fusion cage devices has been reported with static devices, and ours is the first report of an expandable TLIF device failure and posterior migration of one of its components. METHODS: The patient is a 30-year-old man who had previously failed 3 lumbar surgical procedures and presented for L5-S1 lumbar fusion with pedicle screws and transforaminal interbody fusion. RESULTS: Postoperative imaging demonstrated posterior migration of one of the failed expandable interbody components with eventual revision surgery and placement of static transforaminal lumbar interbody fusion cages. CONCLUSION: This is the first case report to describe such complication, and caution must be warranted when using these devices.