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Title: A novel role of sphingosine 1-phosphate receptor S1pr1 in mouse thrombopoiesis
Author: Zhang, Lin
Orban, Martin
Lorenz, Michael
Barocke, Verena
Braun, Daniel
Urtz, Nicole
Schulz, Christian
Von Brühl, Marie-Luise
Tirniceriu, Anca
Gaertner, Florian
Proia, Richard L.
Graf, Thomas
Bolz, Steffen-Sebastian
Montañez, Eloi
Prinz, Marco
Müller, Alexandra
Von Baumgarten, Louisa
Billich, Andreas
Sixt, Michael
Fässler, Reinhard
Von Andrian, Ulrich H.
Junt, Tobias
Massberg, Steffen
Keywords: Metabolisme
Transducció de senyal cel·lular
Cellular signal transduction
Issue Date: 19-Nov-2012
Publisher: Rockefeller University Press
Abstract: Millions of platelets are produced each hour by bone marrow (BM) megakaryocytes (MKs). MKs extend transendothelial proplatelet (PP) extensions into BM sinusoids and shed new platelets into the blood. The mechanisms that control platelet generation remain incompletely understood. Using conditional mutants and intravital multiphoton microscopy, we show here that the lipid mediator sphingosine 1-phosphate (S1P) serves as a critical directional cue guiding the elongation of megakaryocytic PP extensions from the interstitium into BM sinusoids and triggering the subsequent shedding of PPs into the blood. Correspondingly, mice lacking the S1P receptor S1pr1 develop severe thrombocytopenia caused by both formation of aberrant extravascular PPs and defective intravascular PP shedding. In contrast, activation of S1pr1 signaling leads to the prompt release of new platelets into the circulating blood. Collectively, our findings uncover a novel function of the S1P-S1pr1 axis as master regulator of efficient thrombopoiesis and might raise new therapeutic options for patients with thrombocytopenia.
Note: Reproducció del document publicat a:
It is part of: Journal of Experimental Medicine, 2012, vol. 209, num. 12, p. 2165-2181
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ISSN: 0022-1007
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

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