Role of Gas6 in erythropoiesis and anemia in mice.

Détails

ID Serval
serval:BIB_728776889C95
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Role of Gas6 in erythropoiesis and anemia in mice.
Périodique
Journal of Clinical Investigation
Auteur(s)
Angelillo-Scherrer A., Burnier L., Lambrechts D., Fish R.J., Tjwa M., Plaisance S., Sugamele R., DeMol M., Martinez-Soria E., Maxwell P.H., Lemke G., Goff S.P., Matsushima G.K., Earp H.S., Chanson M., Collen D., Izui S., Schapira M., Conway E.M., Carmeliet P.
ISSN
0021-9738
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
118
Numéro
2
Pages
583-596
Langue
anglais
Résumé
Many patients with anemia fail to respond to treatment with erythropoietin (Epo), a commonly used hormone that stimulates erythroid progenitor production and maturation by human BM or by murine spleen. The protein product of growth arrest-specific gene 6 (Gas6) is important for cell survival across several cell types, but its precise physiological role remains largely enigmatic. Here, we report that murine erythroblasts released Gas6 in response to Epo and that Gas6 enhanced Epo receptor signaling by activating the serine-threonine kinase Akt in these cells. In the absence of Gas6, erythroid progenitors and erythroblasts were hyporesponsive to the survival activity of Epo and failed to restore hematocrit levels in response to anemia. In addition, Gas6 may influence erythropoiesis via paracrine erythroblast-independent mechanisms involving macrophages. When mice with acute anemia were treated with Gas6, the protein normalized hematocrit levels without causing undesired erythrocytosis. In a transgenic mouse model of chronic anemia caused by insufficient Epo production, Gas6 synergized with Epo in restoring hematocrit levels. These findings may have implications for the treatment of patients with anemia who fail to adequately respond to Epo.
Mots-clé
Anemia/drug therapy, Anemia/genetics, Animals, Cell Adhesion/genetics, Cell Survival, Disease Models, Animal, Drug Resistance, Erythroblasts/drug effects, Erythroblasts/metabolism, Erythropoiesis/genetics, Erythropoietin/genetics, Erythropoietin/pharmacology, Humans, Intercellular Signaling Peptides and Proteins/genetics, Intercellular Signaling Peptides and Proteins/metabolism, Mice, Mice, Mutant Strains, Oncogene Proteins/genetics, Oncogene Proteins/metabolism, Proto-Oncogene Proteins/metabolism, Proto-Oncogene Proteins c-akt/metabolism, Receptor Protein-Tyrosine Kinases/genetics, Receptor Protein-Tyrosine Kinases/metabolism, Receptors, Erythropoietin/agonists, Recombinant Proteins/genetics, Recombinant Proteins/pharmacology
Pubmed
Web of science
Création de la notice
04/02/2008 16:51
Dernière modification de la notice
03/03/2018 18:17
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