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Title: Renal CD133(+)/CD73(+) progenitors produce erythropoietin under hypoxia and prolyl hydroxylase inhibition
Authors: Bussolati, Benedetta ×
Lauritano, Carola
Moggio, Aldo
Collino, Federica
Mazzone, Max
Camussi, Giovanni #
Issue Date: Jul-2013
Publisher: Williams & Wilkins
Series Title: Journal of the American Society of Nephrology vol:24 issue:8 pages:1234-41
Article number: 10.1681/ASN.2012080772
Abstract: The identity of the peritubular population of cells with mesenchymal phenotype thought responsible for producing erythropoietin in humans remains unclear. Here, renal CD133(+)/CD73(+) progenitor cells, isolated from the human renal inner medulla and described as a population of mesenchymal progenitors, released erythropoietin under hypoxic conditions. CD133(-) cells did not synthesize erythropoietin, and CD133(+) progenitor cells stopped producing erythropoietin when they differentiated and acquired an epithelial phenotype. Inhibition of prolyl hydroxylases, using either dimethyloxalylglycine or a small hairpin RNA against prolyl hydroxylase-2, increased both hypoxia-inducible factor-2α (HIF-2α) expression and erythropoietin transcription. Moreover, under hypoxic conditions, inhibition of prolyl hydroxylase significantly increased erythropoietin release by CD133(+) progenitors. Finally, blockade of HIF-2α impaired erythropoietin synthesis by CD133(+) progenitors. Taken together, these results suggest that it is the renal CD133(+) progenitor cells that synthesize and release erythropoietin under hypoxia, via the prolyl hydroxylase-HIF-2α axis, in the human kidney. In addition, this study provides rationale for the therapeutic use of prolyl hydroxylase inhibitors in the setting of acute or chronic renal injury.
URI: 
ISSN: 1046-6673
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Tumor Inflammation and Angiogenesis (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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