Hepatic HIF-2 regulates erythropoietic responses to hypoxia in renal anemia.

Blood
Pinelopi P KapitsinouVolker H Haase

Abstract

The kidney is the main physiologic source of erythropoietin (EPO) in the adult and responds to decreases in tissue oxygenation with increased EPO production. Although studies in mice with liver-specific or global gene inactivation have shown that hypoxia-inducible factor 2 (Hif-2) plays a major role in the regulation of Epo during infancy and in the adult, respectively, the contribution of renal HIF-2 signaling to systemic EPO homeostasis and the role of extrarenal HIF-2 in erythropoiesis, in the absence of kidney EPO, have not been examined directly. Here, we used Cre-loxP recombination to ablate Hif-2α in the kidney, whereas Hif-2-mediated hypoxia responses in the liver and other Epo-producing tissues remained intact. We found that the hypoxic induction of renal Epo is completely Hif-2 dependent and that, in the absence of renal Hif-2, hepatic Hif-2 takes over as the main regulator of serum Epo levels. Furthermore, we provide evidence that hepatocyte-derived Hif-2 is involved in the regulation of iron metabolism genes, supporting a role for HIF-2 in the coordination of EPO synthesis with iron homeostasis.

References

Mar 1, 1992·The Journal of Clinical Investigation·K U EckardtA Kurtz
Jul 1, 1991·Kidney International·C C TanP J Ratcliffe
Apr 1, 1981·The Journal of Clinical Investigation·E D ZanjaniR C Ash
Dec 1, 1995·Obstetrics and Gynecology·M LevGur, M D Levie
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·G L WangG L Semenza
Jan 20, 1995·The Journal of Biological Chemistry·G L Wang, G L Semenza
Nov 1, 1993·Kidney International·P H MaxwellP J Ratcliffe
Mar 1, 1993·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·S BachmannK U Eckardt
Mar 21, 2000·Genesis : the Journal of Genetics and Development·C Postic, M A Magnuson
Mar 21, 2000·Genesis : the Journal of Genetics and Development·J LiJ A Epstein
Feb 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·V H HaaseR Jaenisch
Oct 23, 2001·Genesis : the Journal of Genetics and Development·L ZhuoA Messing
Jun 29, 2002·Journal of the American Society of Nephrology : JASN·Christian RosenbergerKai-Uwe Eckardt
Oct 30, 2003·The Journal of Biological Chemistry·Christof DameJörg Bungert
May 4, 2004·Nature Reviews. Molecular Cell Biology·Christopher J Schofield, Peter J Ratcliffe
May 15, 2004·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Joachim Fandrey
Jul 9, 2004·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Christina WarneckeKai-Uwe Eckardt
Sep 5, 2006·Seminars in Nephrology·Masaomi Nangaku, Kai-Uwe Eckardt
Sep 15, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Juan C ChavezPaola Pichiule
Feb 8, 2007·Proceedings of the National Academy of Sciences of the United States of America·Michaela GruberM Celeste Simon
Apr 4, 2007·The Journal of Clinical Investigation·Erinn B RankinVolker H Haase
Nov 14, 2007·Methods in Enzymology·Wolfgang Jelkmann
Apr 22, 2008·Cell·Adam T BoutinRandall S Johnson
Jul 9, 2008·Blood·Nancy C Andrews
Apr 9, 2009·The Journal of Clinical Investigation·Maria MastrogiannakiCarole Peyssonnaux

❮ Previous
Next ❯

Citations

Jun 4, 2013·Nature Communications·Shun YamazakiMasayuki Yamamoto
Dec 16, 2011·Nature Reviews. Cancer·Brian KeithM Celeste Simon
Mar 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sanjay C KeswaniAhmet Höke
Apr 19, 2011·The Journal of Biological Chemistry·Erik R AndersonYatrik M Shah
Jan 21, 2012·American Journal of Physiology. Renal Physiology·Pinelopi P KapitsinouVolker H Haase
Nov 15, 2011·The Journal of Clinical Investigation·Yukimi SakodaKoji Tamada
Nov 2, 2012·The Journal of Clinical Investigation·Qingdu LiuVolker H Haase
May 17, 2013·Blood·Maria MastrogiannakiCarole Peyssonnaux
Aug 4, 2011·PloS One·Marta Miró-MurilloJulián Aragonés
Aug 1, 2012·Biologics : Targets & Therapy·Steve Elliott, Angus M Sinclair
Aug 17, 2012·Journal of Visualized Experiments : JoVE·Michael ZimmermanAlmut Grenz
Jan 10, 2014·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Josef Zadrazil, Pavel Horak
Mar 26, 2013·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Alexander S Goldfarb-Rumyantzev, Seth L Alper
May 3, 2014·The Journal of Clinical Investigation·Pinelopi P KapitsinouVolker H Haase
Feb 18, 2014·European Journal of Applied Physiology·Anne-Kristine Meinild LundbyCarsten Lundby
Apr 30, 2014·The Journal of Experimental Medicine·Muhammad Zaeem NomanSalem Chouaib
Jul 6, 2014·European Journal of Applied Physiology·Andrew D GovusPeter Peeling
Aug 12, 2014·Nature Medicine·Min XuJoseph A Garcia
Oct 1, 2014·Pediatric Neurology·Vijayeta Rangarajan, Sandra E Juul
Aug 19, 2014·Nature Genetics·Felipe R LorenzoJosef T Prchal
Oct 2, 2014·Nucleic Acid Therapeutics·Marc T AbramsDominique Stickens
Jul 2, 2011·High Altitude Medicine & Biology·Martha C Tissot van Patot, Max Gassmann
Oct 1, 2015·Expert Opinion on Therapeutic Targets·Nicole RainvilleDon M Wojchowski
May 15, 2015·Biomolecules·Nikolaus Bresgen, Peter M Eckl
Mar 17, 2011·Expert Opinion on Investigational Drugs·Eugene Muchnik, Joshua Kaplan
Jan 6, 2016·The Journal of Clinical Investigation·Yu-Ting ChangShuei-Liong Lin
Nov 17, 2010·The Journal of Physiology·Wolfgang Jelkmann
Sep 24, 2015·Kidney International·Katharina GerlBirgül Kurt
Jul 24, 2012·Trends in Biochemical Sciences·Mei Yee Koh, Garth Powis
Mar 13, 2012·Experimental Cell Research·Volker H Haase
Jul 26, 2011·Biochemical Pharmacology·S ChateauvieuxM Diederich
Sep 16, 2015·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Mario BonominiFrancesco Locatelli
Jun 26, 2014·Cell Biology International·Kazuhiko NishimuraSaburo Matsuo
Mar 2, 2016·The Journal of Clinical Investigation·Navid M FarsijaniVolker H Haase

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anemia

Anemia develops when your blood lacks enough healthy red blood cells. Anemia of inflammation (AI, also called anemia of chronic disease) is a common, typically normocytic, normochromic anemia that is caused by an underlying inflammatory disease. Here is the latest research on anemia.