title: Erythropoietin prevents diabetes-induced podocyte damage.
abstract: OBJECTIVE
  Erythropoietin (EPO) has cytoprotective effects apart from its hematopoietic effects. We studied the effects of different EPO molecules on podocyte signaling in vitro and on podocyte survival in an experimental model of diabetic kidney injury (db/db mouse).
  
  
  METHODS
  We elucidated intracellular signaling by epoetin-beta, darbepoetin-alpha, and the continuous erythropoietin receptor activator (CERA) in immortalized murine podocyte cultures. Moreover, we treated db/db mice with placebo or with CERA in a chronic (14-week) randomized controlled study. We also studied non-diabetic db/m mice as controls.
  
  
  RESULTS
  We could clearly demonstrate phosphorylation of the JAK/PI3K pathway and Akt signaling in podocytes by epoetin-beta, darbepoetin-alpha and CERA. In the long-term animal study we found significantly reduced podocyte numbers in placebo-treated db/db mice compared to db/m control mice (7.4 +/- 0.2 vs. 10.2 +/- 0.9 per glomerular field; p < 0.05). Chronic CERA treatment ameliorated podocyte loss in kidneys of diabetic animals (8.5 +/- 0.5 per glomerular field; p < 0.05 vs. placebo-treated db/db mice).
  
  
  CONCLUSIONS
  EPO activates pro-survival intracellular pathways in podocytes in vitro, and ameliorates diabetes-induced podocyte loss in vivo. Chronic EPO administration may be a feasible way to protect podocyte from diabetic injury.
authors.affiliation: Department of Internal Medicine, Hannover Medical School, Hannover, Germany. schiffer.mario@mh-hannover.de
authors.forename: Mario
authors.initials: M
authors.lastname: Schiffer
authors.forename: Joon-Keun
authors.initials: JK
authors.lastname: Park
authors.forename: Irini
authors.initials: I
authors.lastname: Tossidou
authors.forename: Janina
authors.initials: J
authors.lastname: Bartels
authors.forename: Nelli
authors.initials: N
authors.lastname: Shushakova
authors.forename: Jan
authors.initials: J
authors.lastname: Menne
authors.forename: Danilo
authors.initials: D
authors.lastname: Fliser
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000068256:Darbepoetin alfa; D048909:Diabetes Complications / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology*; D004921:Erythropoietin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D053612:Janus Kinases / Q000378:metabolism; D051379:Mice; D050199:Podocytes / Q000187:drug effects / Q000473:pathology*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction
chemical_list: D011994:Recombinant Proteins; C508420:continuous erythropoietin receptor activator; C103998:epoetin beta; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D011092:Polyethylene Glycols; D053612:Janus Kinases; D051057:Proto-Oncogene Proteins c-akt