Role of Gas6 in erythropoiesis and anemia in mice

被引：86

作者：

Angelillo-Scherrer, Anne ^{[1
,2
]}

Burnier, Laurent ^{[1
,2
]}

Lambrechts, Diether ^{[3
,4
]}

Fish, Richard J.

Tjwa, Marc ^{[3
,4
]}

Plaisance, Stephane ^{[3
,4
]}

Sugamele, Rocco ^{[1
,2
]}

DeMol, Maria ^{[3
,4
]}

Martinez-Soria, Eduardo ^{[5
]}

Maxwell, Patrick H. ^{[6
]}

Lemke, Greg ^{[7
]}

Goff, Stephen P. ^{[8
]}

Matsushima, Glenn K. ^{[9
]}

Earp, H. Shelton ^{[10
]}

Chanson, Marc ^{[11
,12
]}

Collen, Desire ^{[3
,4
]}

Izui, Shozo ^{[5
]}

Schapira, Marc ^{[1
,2
]}

Conway, Edward M. ^{[3
,4
]}

Carmeliet, Peter ^{[3
,4
]}

机构：

[1] Univ Hosp Ctr, Serv & Cent Lab Hematol, CHUV, CH-1011 Lausanne, Switzerland

[2] Univ Lausanne, CH-1011 Lausanne, Switzerland

[3] VIB, Dept Transgene Technol & Gene Therapy, Louvain, Belgium

[4] Katholieke Univ Leuven, Ctr Transgene Technol & Gene Therapy, Louvain, Belgium

[5] Univ Med Ctr, Dept Pathol & Immunol, Geneva, Switzerland

[6] Univ London Imperial Coll Sci Technol & Med, Renal Sect, London, England

[7] Salk Inst Biol Studies, La Jolla, CA 92037 USA

[8] Columbia Univ, Med Ctr, Dept Biochem & Mol Biophys, New York, NY USA

[9] Univ N Carolina, Ctr Neurosci, Chapel Hill, NC USA

[10] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA

[11] Univ Hosp, Dept Pediat, Geneva, Switzerland

[12] Fac Med, Geneva, Switzerland

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2008年 / 118卷 / 02期

关键词：

D O I：

10.1172/JCI30375

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：583 / 596

页数：14

共 55 条

[1] Role of Gas6 receptors in platelet signaling during thrombus stabilization and implications for antithrombotic therapy [J].