Vasopressin stimulates the proliferation and differentiation of red blood cell precursors and improves recovery from anemia

TY - JOUR

T1 - Vasopressin stimulates the proliferation and differentiation of red blood cell precursors and improves recovery from anemia

AU - Mayer, Balázs

AU - Németh, Krisztián

AU - Krepuska, Miklós

AU - Myneni, Vamsee D

AU - Maric, Dragan

AU - Tisdale, John F

AU - Hsieh, Matthew M

AU - Uchida, Naoya

AU - Lee, Heon-Jin

AU - Nemeth, Michael J

AU - Holmbeck, Kenn

AU - Noguchi, Constance Tom

AU - Rogers, Heather

AU - Dey, Soumyadeep

AU - Hansen, Arne

AU - Hong, Jeffrey

AU - Chow, Ian

AU - Key, Sharon

AU - Szalayova, Ildikó

AU - Pagani, Jerome

AU - Markó, Károly

AU - McClain-Caldwell, Ian

AU - Vitale-Cross, Lynn

AU - Young, W Scott

AU - Brownstein, Michael J

AU - Mezey, Éva

N1 - Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

PY - 2017/11/29

Y1 - 2017/11/29

N2 - Arginine vasopressin (AVP) made by hypothalamic neurons is released into the circulation to stimulate water resorption by the kidneys and restore water balance after blood loss. Patients who lack this antidiuretic hormone suffer from central diabetes insipidus. We observed that many of these patients were anemic and asked whether AVP might play a role in red blood cell (RBC) production. We found that all three AVP receptors are expressed in human and mouse hematopoietic stem and progenitor cells. The AVPR1B appears to play the most important role in regulating erythropoiesis in both human and mouse cells. AVP increases phosphorylation of signal transducer and activator of transcription 5, as erythropoietin (EPO) does. After sublethal irradiation, AVP-deficient Brattleboro rats showed delayed recovery of RBC numbers compared to control rats. In mouse models of anemia (induced by bleeding, irradiation, or increased destruction of circulating RBCs), AVP increased the number of circulating RBCs independently of EPO. In these models, AVP appears to jump-start peripheral blood cell replenishment until EPO can take over. We suggest that specific AVPR1B agonists might be used to induce fast RBC production after bleeding, drug toxicity, or chemotherapy.

AB - Arginine vasopressin (AVP) made by hypothalamic neurons is released into the circulation to stimulate water resorption by the kidneys and restore water balance after blood loss. Patients who lack this antidiuretic hormone suffer from central diabetes insipidus. We observed that many of these patients were anemic and asked whether AVP might play a role in red blood cell (RBC) production. We found that all three AVP receptors are expressed in human and mouse hematopoietic stem and progenitor cells. The AVPR1B appears to play the most important role in regulating erythropoiesis in both human and mouse cells. AVP increases phosphorylation of signal transducer and activator of transcription 5, as erythropoietin (EPO) does. After sublethal irradiation, AVP-deficient Brattleboro rats showed delayed recovery of RBC numbers compared to control rats. In mouse models of anemia (induced by bleeding, irradiation, or increased destruction of circulating RBCs), AVP increased the number of circulating RBCs independently of EPO. In these models, AVP appears to jump-start peripheral blood cell replenishment until EPO can take over. We suggest that specific AVPR1B agonists might be used to induce fast RBC production after bleeding, drug toxicity, or chemotherapy.

KW - Anemia/metabolism

KW - Animals

KW - Cell Differentiation/drug effects

KW - Cell Proliferation/drug effects

KW - Erythrocytes/cytology

KW - Humans

KW - Mice

KW - Rats

KW - Receptors, Vasopressin/metabolism

KW - Vasopressins/metabolism

U2 - 10.1126/scitranslmed.aao1632

DO - 10.1126/scitranslmed.aao1632

M3 - Journal article

C2 - 29187641

SN - 1946-6234

VL - 9

JO - Science Translational Medicine

JF - Science Translational Medicine

IS - 418

ER -