Reactivation of Hepatic EPO Synthesis in Mice After PHD Loss
The kidney controls erythropoietin production in adults, and the anemia that can accompany renal failure is a major medical problem. The liver controls erythropoietin production during fetal life but is silenced shortly after birth. Erythropoietin transcription is controlled by hypoxia-inducible fac...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2010-07, Vol.329 (5990), p.407-407 |
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| creator | Minamishima, Yoji Andrew Kaelin, William G. Jr |
| description | The kidney controls erythropoietin production in adults, and the anemia that can accompany renal failure is a major medical problem. The liver controls erythropoietin production during fetal life but is silenced shortly after birth. Erythropoietin transcription is controlled by hypoxia-inducible factor (HIF), which is inhibited by three prolyl hydroxylases (PHD1, PHD2, and PHD3). Systemic PHD2 inactivation has been found to increase renal, but not hepatic, erythropoietin production. In contrast, we show here that simultaneous genetic inactivation of all three PHD paralogs in mice reactivates hepatic erythropoietin production and stimulates red blood synthesis, suggesting that pan-PHD inhibitory drugs might be useful for the treatment of anemia caused by chronic kidney disease. |
| doi_str_mv | 10.1126/science.1192811 |
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Jr</creator><creatorcontrib>Minamishima, Yoji Andrew ; Kaelin, William G. Jr</creatorcontrib><description>The kidney controls erythropoietin production in adults, and the anemia that can accompany renal failure is a major medical problem. The liver controls erythropoietin production during fetal life but is silenced shortly after birth. Erythropoietin transcription is controlled by hypoxia-inducible factor (HIF), which is inhibited by three prolyl hydroxylases (PHD1, PHD2, and PHD3). Systemic PHD2 inactivation has been found to increase renal, but not hepatic, erythropoietin production. In contrast, we show here that simultaneous genetic inactivation of all three PHD paralogs in mice reactivates hepatic erythropoietin production and stimulates red blood synthesis, suggesting that pan-PHD inhibitory drugs might be useful for the treatment of anemia caused by chronic kidney disease.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1192811</identifier><identifier>PMID: 20651146</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Anemia ; Anemia - drug therapy ; Anemia - etiology ; Anemias ; Animals ; Biological and medical sciences ; Biosynthesis ; Blood ; BREVIA ; Control equipment ; Epics ; Erythrocytes ; Erythropoiesis ; Erythropoietin - biosynthesis ; Erythropoietin - genetics ; Fundamental and applied biological sciences. Psychology ; Genetics ; Genotypes ; Glycoproteins ; Hematocrit ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Hypoxia-Inducible Factor-Proline Dioxygenases ; Inactivation ; Kidney diseases ; Kidney Failure, Chronic - complications ; Kidneys ; Liver ; Liver - enzymology ; Liver - metabolism ; Mice ; Procollagen-Proline Dioxygenase - antagonists & inhibitors ; Procollagen-Proline Dioxygenase - genetics ; Procollagen-Proline Dioxygenase - metabolism ; Reverse transcriptase polymerase chain reaction ; Rodents ; Synthesis ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Vertebrates: blood, hematopoietic organs, reticuloendothelial system</subject><ispartof>Science (American Association for the Advancement of Science), 2010-07, Vol.329 (5990), p.407-407</ispartof><rights>2010 American Association for the Advancement of Science</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2010, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c594t-bfb18b95213a7409c8caefa3df275ad360070d26458dabceccf9d1978376b00f3</citedby><cites>FETCH-LOGICAL-c594t-bfb18b95213a7409c8caefa3df275ad360070d26458dabceccf9d1978376b00f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/40731982$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/40731982$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,780,784,803,885,2884,2885,27924,27925,58017,58250</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23041408$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20651146$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Minamishima, Yoji Andrew</creatorcontrib><creatorcontrib>Kaelin, William G. Jr</creatorcontrib><title>Reactivation of Hepatic EPO Synthesis in Mice After PHD Loss</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>The kidney controls erythropoietin production in adults, and the anemia that can accompany renal failure is a major medical problem. The liver controls erythropoietin production during fetal life but is silenced shortly after birth. Erythropoietin transcription is controlled by hypoxia-inducible factor (HIF), which is inhibited by three prolyl hydroxylases (PHD1, PHD2, and PHD3). Systemic PHD2 inactivation has been found to increase renal, but not hepatic, erythropoietin production. In contrast, we show here that simultaneous genetic inactivation of all three PHD paralogs in mice reactivates hepatic erythropoietin production and stimulates red blood synthesis, suggesting that pan-PHD inhibitory drugs might be useful for the treatment of anemia caused by chronic kidney disease.</description><subject>Anemia</subject><subject>Anemia - drug therapy</subject><subject>Anemia - etiology</subject><subject>Anemias</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biosynthesis</subject><subject>Blood</subject><subject>BREVIA</subject><subject>Control equipment</subject><subject>Epics</subject><subject>Erythrocytes</subject><subject>Erythropoiesis</subject><subject>Erythropoietin - biosynthesis</subject><subject>Erythropoietin - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetics</subject><subject>Genotypes</subject><subject>Glycoproteins</subject><subject>Hematocrit</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>Hypoxia-Inducible Factor-Proline Dioxygenases</subject><subject>Inactivation</subject><subject>Kidney diseases</subject><subject>Kidney Failure, Chronic - complications</subject><subject>Kidneys</subject><subject>Liver</subject><subject>Liver - enzymology</subject><subject>Liver - metabolism</subject><subject>Mice</subject><subject>Procollagen-Proline Dioxygenase - antagonists & inhibitors</subject><subject>Procollagen-Proline Dioxygenase - genetics</subject><subject>Procollagen-Proline Dioxygenase - metabolism</subject><subject>Reverse transcriptase polymerase chain reaction</subject><subject>Rodents</subject><subject>Synthesis</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Vertebrates: blood, hematopoietic organs, reticuloendothelial system</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kVtrFDEYhoNY7LZ67ZU6FERvxn45TA4gQqmtK6y0WHsdMpmkzTI72Sazhf57U3ZcDxdeJeF98pB8L0IvMXzAmPDjbIMbrCsHRSTGT9AMg2pqRYA-RTMAymsJotlHBzkvAUqm6DO0T4A3GDM-Qx-_O2PHcG_GEIcq-mru1mVvq7PLi-rqYRhvXQ65CkP1LVhXnfjRpepy_rlaxJyfoz1v-uxeTOshuj4_-3E6rxcXX76enixq2yg21q1vsWxVQzA1goGy0hrnDe08EY3pKAcQ0BHOGtmZ1jprveqwEpIK3gJ4eog-bb3rTbtynXXDmEyv1ymsTHrQ0QT9dzKEW30T7zXlXDaMFsG7SZDi3cblUa9Ctq7vzeDiJmtBGYDkXBTy_X9JTCTlQnCiCnr0D7qMmzSUQWhOCVWYiEff8RayqQwsOb97NQb9WKGeKtRTheXG6z8_u-N_dVaAtxNgsjW9T2awIf_mKDDMQBbu1ZZb5jGmXc5AUKwkKfmbbe5N1OYmFcf1FQFMAUsBlDX0JwlatqA</recordid><startdate>20100723</startdate><enddate>20100723</enddate><creator>Minamishima, Yoji Andrew</creator><creator>Kaelin, William G. 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| subjects | Anemia Anemia - drug therapy Anemia - etiology Anemias Animals Biological and medical sciences Biosynthesis Blood BREVIA Control equipment Epics Erythrocytes Erythropoiesis Erythropoietin - biosynthesis Erythropoietin - genetics Fundamental and applied biological sciences. Psychology Genetics Genotypes Glycoproteins Hematocrit Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Hypoxia-Inducible Factor-Proline Dioxygenases Inactivation Kidney diseases Kidney Failure, Chronic - complications Kidneys Liver Liver - enzymology Liver - metabolism Mice Procollagen-Proline Dioxygenase - antagonists & inhibitors Procollagen-Proline Dioxygenase - genetics Procollagen-Proline Dioxygenase - metabolism Reverse transcriptase polymerase chain reaction Rodents Synthesis Transcription Factors - genetics Transcription Factors - metabolism Vertebrates: blood, hematopoietic organs, reticuloendothelial system |
| title | Reactivation of Hepatic EPO Synthesis in Mice After PHD Loss |
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