Universidad Peruana Cayetano Heredia

HIF-1α is a protective factor in conditional PHD2-βdeficient mice suffering from severe HIF-2-induced excessive erythropoiesis

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dc.contributor.author Franke, Kristin
dc.contributor.author Kalucka, Joanna
dc.contributor.author Mamlouk, Soulafa
dc.contributor.author Singh, Rashim Pal
dc.contributor.author Muschter, Antje
dc.contributor.author Weidemann, Alexander
dc.contributor.author Iyengar, Vasuprada
dc.contributor.author Jahn, Steffen
dc.contributor.author Wieczorek, Kathrin
dc.contributor.author Geiger, Kathrin
dc.contributor.author Muders, Michaels
dc.contributor.author Sykes, Alex M.
dc.contributor.author Poitz, David M.
dc.contributor.author Ripich, Tatsiana
dc.contributor.author Otto, Teresa
dc.contributor.author Bergmann, Sybille
dc.contributor.author Breier, Georg
dc.contributor.author Baretton, Gustavo
dc.contributor.author Fong, Guo-Hua
dc.contributor.author Greaves, David R.
dc.contributor.author Bornstein, Stefan
dc.contributor.author Chavakis, Triantafyllos
dc.contributor.author Joachim Fandrey, Max Gassmann
dc.contributor.author Wielockx, Ben
dc.date.accessioned 2022-01-04T20:29:54Z
dc.date.available 2022-01-04T20:29:54Z
dc.date.issued 2013
dc.identifier.uri https://hdl.handle.net/20.500.12866/10391
dc.description.abstract Erythropoiesis must be tightly balanced to guarantee adequate oxygen delivery to all tissues in the body. This process relies predominantly on the hormone erythropoietin (EPO) and its transcription factor hypoxia inducible factor (HIF). Accumulating evidence suggests that oxygen-sensitive prolyl hydroxylases (PHDs) are important regulators of this entire system. Here, we describe a novel mouse line with conditional PHD2 inactivation (cKO P2) in renal EPO producing cells, neurons, and astrocytes that displayed excessive erythrocytosis because of severe overproduction of EPO, exclusively driven by HIF-2α. In contrast, HIF-1α served as a protective factor, ensuring survival of cKO P2 mice with HCT values up to 86%. Using different genetic approaches, we show that simultaneous inactivation of PHD2 and HIF-1α resulted in a drastic PHD3 reduction with consequent overexpression of HIF-2α-related genes, neurodegeneration, and lethality. Taken together, our results demonstrate for the first time that conditional loss of PHD2 in mice leads to HIF-2α–dependent erythrocytosis, whereas HIF-1α protects these mice, providing a platform for developing new treatments of EPO-related disorders, such as anemia. en_US
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartofseries Blood
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Erythrocytosis en_US
dc.subject erythropoiesis en_US
dc.subject mice en_US
dc.subject protective factors en_US
dc.subject heart sound p2 en_US
dc.subject kidney en_US
dc.subject nerve degeneration en_US
dc.title HIF-1α is a protective factor in conditional PHD2-βdeficient mice suffering from severe HIF-2-induced excessive erythropoiesis en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1182/blood-2012-08-449181
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.06
dc.relation.issn 1528-0020


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