NDLI: Role of Gas6 in erythropoiesis and anemia in mice

Content Provider	PubMed Central
Author	Anne, Angelillo-scherrer Burnier, Laurent Lambrechts, Diether Fish, Richard J. Marc, Tjwa Plaisance, Stéphane Rocco, Sugamele Demol, Maria Martinez Soria, Eduardo Maxwell, Patrick H. Lemke, Greg Goff, Stephen P. Matsushima, Glenn K. Earp, H. Shelton Chanson, Marc Collen, Désiré Izui, Shozo Schapira, Marc Conway, Edward M. Carmeliet, Peter
Copyright Year	2008
Abstract	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.
Related Links	http://dx.doi.org/10.1172/JCI30375
Starting Page	583
File Format	PDF
ISSN	00219738
Journal	The Journal of Clinical Investigation
Issue Number	2
Volume Number	118
Language	English
Publisher	American Society for Clinical Investigation
Publisher Date	2008-02-01
Access Restriction	Open
Rights Holder	American Society for Clinical Investigation
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Medicine

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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