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). CONCLUSION: 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. Copyright 2008 S. Karger AG, Basel.
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). CONCLUSION: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. Copyright 2008 S. Karger AG, Basel.
Authors: Tamadher A Alghamdi; Syamantak Majumder; Karina Thieme; Sri N Batchu; Kathryn E White; Youan Liu; Angela S Brijmohan; Bridgit B Bowskill; Suzanne L Advani; Minna Woo; Andrew Advani Journal: J Am Soc Nephrol Date: 2017-04-19 Impact factor: 10.121
Authors: Aihua Deng; Mary Ann K Arndt; Joseph Satriano; Prabhleen Singh; Timo Rieg; Scott Thomson; Tong Tang; Roland C Blantz Journal: Am J Physiol Renal Physiol Date: 2010-09-29
Authors: Robert Faulhaber-Walter; Lanping Jiang; Diane Mizel; Patricia M Zerfas; Jeffrey B Kopp; Jurgen B Schnermann; Limeng Chen; Mario Schiffer Journal: Int J Nephrol Renovasc Dis Date: 2020-02-21