Angelillo-Scherrer, A and Burnier, L and Lambrechts, D and Fish, RJ and Tjwa, M and Plaisance, S and Sugamele, R and DeMol, M and Martinez-Soria, E and Maxwell, PH and Lemke, G and Goff, SP and Matsushima, GK and Earp, HS and Chanson, M and Collen, D and Izui, S and Schapira, M and Conway, EM and Carmeliet, P (2008) Role of Gas6 in erythropoiesis and anemia in mice. J Clin Invest , 118 (2) 583 - 596. 10.1172/JCI30375.
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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.
|Title:||Role of Gas6 in erythropoiesis and anemia in mice.|
|Additional information:||PMCID: PMC2176185|
|Keywords:||Anemia, Animals, Cell Adhesion, Cell Survival, Disease Models, Animal, Drug Resistance, Erythroblasts, Erythropoiesis, Erythropoietin, Humans, Intercellular Signaling Peptides and Proteins, Mice, Mice, Mutant Strains, Oncogene Proteins, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Receptor Protein-Tyrosine Kinases, Receptors, Erythropoietin, Recombinant Proteins|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)|
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