Roles of renal erythropoietin-producing (REP) cells in the maintenance of systemic oxygen homeostasis

Invited Review
First Online:
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Revised:
Accepted:

Abstract

Erythropoietic induction is critical for enhancing the efficiency of oxygen delivery during the chronic phase of the systemic hypoxia response. The erythroid growth factor erythropoietin (Epo) triggers the erythropoietic induction through the activation of erythroid genes related to cell survival, differentiation, and iron metabolism. Because Epo is produced in renal Epo-producing (REP) cells in a hypoxia-inducible manner, REP cells serve as a control center for the systemic hypoxia response. In fact, the loss of Epo production in REP cells causes chronic severe anemia in genetically modified mice, and REP cell-specific inactivation of PHD2 (prolyl-hydroxylase domain enzyme 2) results in erythrocytosis via overexpression of the Epo gene due to the constitutive activation of HIF2α (hypoxia-inducible transcription factor 2α). REP cells are located in the interstitial spaces between renal tubules and capillaries, where the oxygen supply is low but oxygen consumption is high, for the highly sensitive detection of decreased oxygen supplies to the body. Under disease conditions, REP cells transform to myofibroblasts and lose their Epo-producing ability. Therefore, elucidation of Epo gene regulation and REP cell features directly contributes to understanding the pathology of chronic kidney disease. To further analyze REP cells, we introduce a newly established mouse line in which REP cells are efficiently labeled with fluorescent protein.

Keywords

Anemia Hypoxia PHD-HIF cascade Genetically modified mice 
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Notes

Acknowledgments

We appreciate Dr. Yasuo Mori (Kyoto University) for giving us the opportunity to introduce our research project. This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas “Oxygen biology (No. 26111002)” from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  1. 1.Division of Interdisciplinary Medical Science, Center for Oxygen Medicine, United Centers for Advanced Research and Translational MedicineTohoku University Graduate School of MedicineSendaiJapan
  2. 2.Department of Medical BiochemistryTohoku University Graduate School of MedicineSendaiJapan

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