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This Article Full Text Full Text (PDF) All Versions of this Article: 295/6/F1689    most recent 90333.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Breggia, A. C. Articles by Himmelfarb, J. Search for Related Content PubMed PubMed Citation Articles by Breggia, A. C. Articles by Himmelfarb, J.

JAK2/Y343/STAT5 signaling axis is required for erythropoietin-mediated protection against ischemic injury in primary renal tubular epithelial cells

¹Clinical and Translational Research, ²Center for Molecular Biology, Stem and Progenitor Cell Biology, Maine Medical Center Research Institute, Scarborough; and ³Division of Nephrology and Transplantation, Department of Medicine, Maine Medical Center, Portland, Maine

Submitted 29 May 2008 ; accepted in final form 21 September 2008

Erythropoietin has emerged as a potential therapy for the treatment of ischemic tissue injury. In erythroid cells, the JAK2/Y343/STAT5 signaling axis has been shown to be necessary for stress but not steady-state erythropoiesis. The requirement for STAT5 activation in erythropoietin-mediated protection from ischemic injury has not been well-studied. To answer this question, we induced reproducible necrotic ischemic injury in primary mouse renal tubular epithelial cells (RTEC) in vitro. Using RTEC from erythropoietin receptor mutant mice with differential STAT5 signaling capabilities, we demonstrated first, that EPO administration either before or during injury significantly protects against mild-moderate but not severe necrotic cell death; and second, the JAK2/Y343/STAT5 signaling axis is required for protection against ischemic injury in primary mouse RTEC. In addition, we identified Pim-3, a prosurvival STAT5 target gene, as responsive to EPO in the noninjured kidney both in vitro and in vivo.

hypoxia; ischemic preconditioning