Difference between revisions of "Farsijani 2016 J Clin Invest"
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{{Publication | {{Publication | ||
|title=Farsijani NM, Liu Q, Kobayashi H, Davidoff O, Sha F, Fandrey J, Ikizler TA, O'Connor PM, Haase VH (2016) Renal epithelium regulates erythropoiesis via HIF-dependent suppression of erythropoietin. J Clin Invest 126:1425-37. Β | |title=Farsijani NM, Liu Q, Kobayashi H, Davidoff O, Sha F, Fandrey J, Ikizler TA, O'Connor PM, Haase VH (2016) Renal epithelium regulates erythropoiesis via HIF-dependent suppression of erythropoietin. J Clin Invest 126:1425-37. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/26927670 PMID: 26927670 Open Access] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/26927670 PMID: 26927670 Open Access] | ||
|authors=Farsijani NM, Liu Q, Kobayashi H, Davidoff O, Sha F, Fandrey J, Ikizler TA, O'Connor PM, Haase VH | |authors=Farsijani NM, Liu Q, Kobayashi H, Davidoff O, Sha F, Fandrey J, Ikizler TA, O'Connor PM, Haase VH | ||
|year=2016 | |year=2016 | ||
|journal=J Clin Invest | |journal=J Clin Invest | ||
|abstract=The adult kidney plays a central role in erythropoiesis and is the main source of erythropoietin (EPO), an oxygen-sensitive glycoprotein that is essential for red blood cell production. Decreases of renal | |abstract=The adult kidney plays a central role in erythropoiesis and is the main source of erythropoietin (EPO), an oxygen-sensitive glycoprotein that is essential for red blood cell production. Decreases of renal pO<sub>2</sub> promote hypoxia-inducible factor 2-mediated (HIF-2-mediated) induction of EPO in peritubular interstitial fibroblast-like cells, which serve as the cellular site of EPO synthesis in the kidney. It is not clear whether HIF signaling in other renal cell types also contributes to the regulation of EPO production. Here, we used a genetic approach in mice to investigate the role of renal epithelial HIF in erythropoiesis. Specifically, we found that HIF activation in the proximal nephron via induced inactivation of the von Hippel-Lindau tumor suppressor, which targets the HIF-Ξ± subunit for proteasomal degradation, led to rapid development of hypoproliferative anemia that was associated with a reduction in the number of EPO-producing renal interstitial cells. Moreover, suppression of renal EPO production was associated with increased glucose uptake, enhanced glycolysis, reduced mitochondrial mass, diminished O<sub>2</sub> consumption, and elevated renal tissue pO<sub>2</sub>. Our genetic analysis suggests that tubulointerstitial cellular crosstalk modulates renal EPO production under conditions of epithelial HIF activation in the kidney. | ||
|mipnetlab=JP Sagamihara Kobayashi H | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |area=Respiration, Genetic knockout;overexpression | ||
|organism=Mouse | |||
|tissues=Nervous system | |||
|preparations=Permeabilized tissue | |||
|injuries=Oxidative stress;RONS | |||
|couplingstates=LEAK, OXPHOS | |||
|substratestates=CI, CII, CIV, ROX | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=Labels, 2016-04 | |additional=Labels, 2016-04 | ||
}} | }} |
Revision as of 15:25, 4 April 2016
Farsijani NM, Liu Q, Kobayashi H, Davidoff O, Sha F, Fandrey J, Ikizler TA, O'Connor PM, Haase VH (2016) Renal epithelium regulates erythropoiesis via HIF-dependent suppression of erythropoietin. J Clin Invest 126:1425-37. |
Farsijani NM, Liu Q, Kobayashi H, Davidoff O, Sha F, Fandrey J, Ikizler TA, O'Connor PM, Haase VH (2016) J Clin Invest
Abstract: The adult kidney plays a central role in erythropoiesis and is the main source of erythropoietin (EPO), an oxygen-sensitive glycoprotein that is essential for red blood cell production. Decreases of renal pO2 promote hypoxia-inducible factor 2-mediated (HIF-2-mediated) induction of EPO in peritubular interstitial fibroblast-like cells, which serve as the cellular site of EPO synthesis in the kidney. It is not clear whether HIF signaling in other renal cell types also contributes to the regulation of EPO production. Here, we used a genetic approach in mice to investigate the role of renal epithelial HIF in erythropoiesis. Specifically, we found that HIF activation in the proximal nephron via induced inactivation of the von Hippel-Lindau tumor suppressor, which targets the HIF-Ξ± subunit for proteasomal degradation, led to rapid development of hypoproliferative anemia that was associated with a reduction in the number of EPO-producing renal interstitial cells. Moreover, suppression of renal EPO production was associated with increased glucose uptake, enhanced glycolysis, reduced mitochondrial mass, diminished O2 consumption, and elevated renal tissue pO2. Our genetic analysis suggests that tubulointerstitial cellular crosstalk modulates renal EPO production under conditions of epithelial HIF activation in the kidney.
β’ O2k-Network Lab: JP Sagamihara Kobayashi H
Labels: MiParea: Respiration, Genetic knockout;overexpression
Stress:Oxidative stress;RONS Organism: Mouse Tissue;cell: Nervous system Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS
HRR: Oxygraph-2k
Labels, 2016-04