Abstract
BackgroundLike other steroid hormones, vitamin D elicits both transcriptional events and rapid non genomic effects. Vitamin D receptor (VDR) localization and mechanisms of VDR-triggered non genomic responses are still controversial. Although anticoagulant effects of vitamin D have been reported and VDR signalling has been characterized in monocytes and vascular cells, nothing is known about VDR expression and functions in human platelets, anucleated fragments of megakaryocytes which are known targets of other steroids.Methodology/Principal FindingsIn this study we characterized the expression and cellular localization of VDR in human platelets and in a megakaryocyte lineage. Human platelets and their TPA-differentiated precursors expressed a classical 50 kDa VDR protein, which increased with megakaryocytes maturation. By biochemical fractionation studies we demonstrated the presence of the receptor in the soluble and mitochondrial compartment of human platelets, and the observation was confirmed by immunoelectron microscopy analysis. Similar localization was found in mature megakaryocytes, where besides its classical nuclear localization the receptor was evident as soluble and mitochondria resident protein.ConclusionsThe results reported here suggest that megakaryocytopoiesis and platelet activation, which are calcium-dependent events, might be modulated by a mitochondrial non genomic activity of VDR. These data open challenging future studies on VDR physiological role in platelets and more generally in mitochondria.
Highlights
The vitamin D endocrine system plays a crucial role in calcium homeostasis and bone metabolism [1,2]
While it is clear that the Vitamin D receptor (VDR)/vitamin D system plays an important role in maintaining normal antithrombotic homeostasis in vivo, nothing is known about VDR expression and function in platelets, the main players in thrombus formation
We found that human platelets express VDR, which is mainly located in the mitochondrial compartment
Summary
The vitamin D endocrine system plays a crucial role in calcium homeostasis and bone metabolism [1,2]. In addition to vitamin D classical target tissues, VDR is expressed in monocytic cells [16] and vascular endothelial cells [17], suggesting potential roles of vitamin D in antithrombotic functions It has been demonstrated the anticoagulant effects of vitamin D in terms of up-regulation of thrombomodulin and down-regulation of coagulation tissue factor in monocytes [16,18] and in vivo in aorta, liver and kidney [19]. Cytoplasmic fragments rich in mitochondria are released and form proplatelets These structural changes are accompanied by progressive expression of adhesive glycoprotein complexes implicated in platelet function and by increases in Ca2+ mobilization and Ca2+ influx by the Gq-coupled receptor agonists, thrombin and thromboxane A2 [20]. Anticoagulant effects of vitamin D have been reported and VDR signalling has been characterized in monocytes and vascular cells, nothing is known about VDR expression and functions in human platelets, anucleated fragments of megakaryocytes which are known targets of other steroids
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