Erythropoietin prevents diabetes-induced podocyte damage.
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.
Schiffer
Mario
M
Department of Internal Medicine, Hannover Medical School, Hannover, Germany. schiffer.mario@mh-hannover.de
Park
Joon-Keun
JK
Tossidou
Irini
I
Bartels
Janina
J
Shushakova
Nelli
N
Menne
Jan
J
Fliser
Danilo
D
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
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