Co-localization of erythropoietin mRNA and ecto-5'-nucleotidase immunoreactivity in peritubular cells of rat renal cortex indicates that fibroblasts produce erythropoietin.

Bachmann, S.; Hir, Michel Le; Eckardt, Kai‐Uwe

doi:10.1177/41.3.8429197

Cited by 303 publications

(212 citation statements)

References 14 publications

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“…The anemia results from decreased TfR expression in erythroid precursor cells (34). Interstitial fibroblasts in the kidney respond to hypoxia that results from decreased red cell oxygen-carrying capacity by secreting erythropoietin (37,38), and erythropoietin levels increase three-to fivefold in animals that lack IRP2, as expected in response to anemia (34).…”

Section: Renal Regulation Of Ferritin and Tfr Expression: Role Of Iromentioning

confidence: 79%

Renal Iron Metabolism

Zhang¹,

Meyron-Holtz²,

Rouault³

2007

Journal of the American Society of Nephrology

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Section: Renal Regulation Of Ferritin and Tfr Expression: Role Of Iromentioning

confidence: 79%

Renal Iron Metabolism

Zhang¹,

Meyron-Holtz²,

Rouault³

2007

Journal of the American Society of Nephrology

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“…REP cells express the interstitial fibroblast marker CD73 and neuronal markers, such as microtubule-associated protein 2 and neurofilament light polypeptide [19][20][21]44,45 . Neural crest-derived cells distribute in the interstitial space of renal tubules in adult mice 45 .…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin production in neuroepithelial and neural crest cells during primitive erythropoiesis

et al. 2013

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Erythropoietin (Epo) supports both primitive erythropoiesis in the yolk sac and definitive erythropoiesis in the fetal liver and bone marrow. Although definitive erythropoiesis requires kidney-and liver-secreted Epo, it is unclear which cells produce Epo for primitive erythropoiesis. Here we find neural Epo-producing (NEP) cells in mid-gestational stage embryos using mouse lines that express green fluorescent protein (GFP) under the Epo gene regulation. In these mice, GFP is expressed exclusively in a subpopulation of neural and neural crest cells at embryonic day 9.0 when Epo-deficient embryos exhibit abnormalities in primitive erythropoiesis. The GFP-positive NEP cells express Epo mRNA and the ex vivo culture of embryonic day 8.5 neural tubes results in the secretion of Epo, which is able to induce the proliferation and differentiation of yolk sac-derived erythroid cells. These results thus suggest that NEP cells secrete Epo and might support the development of primitive erythropoiesis.

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“…When hematocrit is in the normal range, the kidney produces a low level of EPO, with EPO expression limited to a small number of these fibroblasts in the deep cortex and superficial outer medulla [2][3][4]. The increased production of EPO under anemic circumstances involves progressive recruitment of additional interstitial fibroblasts in a pattern that spreads outward from the deep cortex toward the capsule and the inner medulla.…”

Section: Mechanisms Of Renal Erythropoietin Productionmentioning

confidence: 99%

Hypoxia and the HIF system in kidney disease

2007

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The kidney is sensitive to changes in oxygen delivery. This sensitivity has the merit of facilitating the kidneys in their adjustment of erythropoietin (EPO) production to changes in oxygen supply. The main determinant of EPO synthesis is the transcriptional activity of its gene in kidneys, which is related to local oxygen tensions. Regulation of EPO production is mediated by hypoxia-inducible factor (HIF). When local oxygen tension decreases, accumulated HIF binds to the key sequence of the EPO gene, the hypoxia-responsive element (HRE), and activates transcription of EPO. HIF consists of a constitutive β-subunit and one of alternative oxygen-regulated HIF α-subunits (HIF-1α, HIF-2α, and HIF-3α), and HIF-2α is responsible for erythropoietin production. However, the high sensitivity to changes in oxygen tension also makes the kidney prone to hypoxic injury. Severe energy depletion and subsequent activation of a number of critical alterations in metabolism occurs under hypoxic conditions. Hypoxia is also a profibrogenic stimulus. In addition to ischemic acute renal failure, hypoxia can also play a crucial role in the development of nephrotoxic acute kidney injury, radiocontrast nephropathy, and acute glomerulonephritis. Furthermore, accumulating evidence suggests that chronic hypoxia is a final common pathway to end-stage kidney failure in chronic kidney disease. Given that renal hypoxia has pivotal roles on the development and progression of both acute and chronic kidney disease, hypoxia can be a valid therapeutic target for chronic kidney disease. Activation of HIF leads to expression of a variety of adaptive genes in a coordinated manner. Studies utilizing HIF-stimulating agents proved efficacy in various kidney disease models, suggesting that HIF activation is an ideal target of future therapeutic approaches.

show abstract

Co-localization of erythropoietin mRNA and ecto-5'-nucleotidase immunoreactivity in peritubular cells of rat renal cortex indicates that fibroblasts produce erythropoietin.

Cited by 303 publications

References 14 publications

Renal Iron Metabolism

Renal Iron Metabolism

Erythropoietin production in neuroepithelial and neural crest cells during primitive erythropoiesis

Hypoxia and the HIF system in kidney disease

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