title: Controlled regulation of erythropoietin by primary cultured renal cells for renal failure induced anemia.
abstract: OBJECTIVE
  Renal failure induced anemia develops as a result of inadequate production of erythropoietin, which is the primary regulator of red blood cell production. We previously noted that culture expanded primary renal cells stably express erythropoietin and suggested that these cells may be used as a potential treatment for renal failure induced anemia. We investigated whether these cells are able to regulate erythropoietin expression in a controlled manner under different oxygen and environmental conditions.
  
  
  METHODS
  Primary rat renal cells were exposed to different hypoxic (0.1% to 1% O(2)) and normoxic environments. Erythropoietin expression was assessed using reverse transcriptase-polymerase chain reaction. Erythropoietin production was measured in culture medium using Meso Scale Discovery® assays. Results were plotted to compare different levels of production to the control.
  
  
  RESULTS
  Cultured renal cells expressed high levels of erythropoietin under hypoxia for up to 24 hours with a gradual decrease thereafter. However, erythropoietin expression was decreased when cells were switched from a hypoxic to a normoxic environment within the initial 24 hours. This indicated that cultured renal cells have the capacity to sense environmental oxygen tension and regulate erythropoietin expression accordingly. In addition, erythropoietin release in medium followed a pattern similar to that of gene expression under normoxic and hypoxic conditions.
  
  
  CONCLUSIONS
  These findings indicate that primary renal cells have the ability to regulate erythropoietin gene expression and release through environment dependent mechanisms. This also suggests that with further study the possibility exists of developing these cells as a potential method to treat renal failure induced anemia.
authors.affiliation: Wake Forest Institute for Regenerative Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Gyabaah
authors.forename: Tamer
authors.initials: T
authors.lastname: Aboushwareb
authors.forename: Nadia
authors.initials: N
authors.lastname: Guimaraes Souza
authors.forename: Liliya
authors.initials: L
authors.lastname: Yamaleyeva
authors.forename: Adam
authors.initials: A
authors.lastname: Varner
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Wang
authors.forename: Anthony
authors.initials: A
authors.lastname: Atala
authors.forename: James J
authors.initials: JJ
authors.lastname: Yoo
mesh_terms: D000740:Anemia / Q000209:etiology*; D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D004921:Erythropoietin / Q000502:physiology*; D007668:Kidney / Q000166:cytology*; D007676:Kidney Failure, Chronic / Q000150:complications*; D051381:Rats
chemical_list: D004921:Erythropoietin