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Communication Dans Un Congrès Année : 2009

Autocrine vitamine K dependent proteins regulate neural stem cells proliferation

Résumé

The adult mammalian brain hosts neural stem cells (NSC) within the subventricular zone (SVZ). Although many studies have identified exogenous mechanisms of NSC control, the endogenous mechanisms regulating the neurogenic activity of NSC have only poorly been explored. Vitamin K-dependent proteins (VKDP) are a family of secreted proteins in which some glutamyl residues are post-translationally modified to γ-carboxyglutamic acid residues. This enzymatic reaction requires vitamin K and is necessary for the secretion and/or activity of vitamin K-dependent proteins. Warfarin, a widely used anticoagulant, antagonizes vitamin K and thereby blocks functional VKDP production. Mainly known for their role in coagulation, vitamin K-dependent proteins have recently been shown to regulate proliferation and differentiation on various cell types. In the present study, we investigated both in vitro and in vivo possible involvement of vitamin K-dependent proteins in the regulation of NSC proliferation and differentiation. Blockade of functional vitamin K-dependent proteins production, using the anti-coagulant warfarin, promoted SVZ cells proliferation in vitro and in vivo. Mechanisms underlying warfarin effects were next analyzed in vitro. Vitamin K as well as VKDP released by SVZ cells in conditioned media reversed warfarin effects, suggesting that secreted endogenous VKDP restrain SVZ cells proliferation. RT-PCR, Western blot and immunochemistry analyses revealed that neural stem cells express two secreted VKDP, protein-S and Gas 6, and their receptors Axl, Tyro-3 and Mer. Exogenous Gas-6 addition affected neither basal nor warfarin promoted growth of SVZ cells. Conversely, protein-S inhibited SVZ cell proliferation and reversed warfarin growth promoting activity. Our study identifies vitamin K-dependent proteins as major actors in the control of the SVZ neurogenesis and opens new insights in the regulation of stem cells activity by vascular determinants.
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Dates et versions

hal-00456044 , version 1 (11-02-2010)

Identifiants

  • HAL Id : hal-00456044 , version 1

Citer

Valérie Coronas. Autocrine vitamine K dependent proteins regulate neural stem cells proliferation. 3rd Mediterranean Conference of Neuroscience, 2009, Alexandrie, Egypt. ⟨hal-00456044⟩

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