PMID- 18815218 OWN - NLM STAT- MEDLINE DCOM- 20090312 LR - 20190104 IS - 1931-857X (Print) IS - 1522-1466 (Electronic) IS - 1522-1466 (Linking) VI - 295 IP - 6 DP - 2008 Dec TI - JAK2/Y343/STAT5 signaling axis is required for erythropoietin-mediated protection against ischemic injury in primary renal tubular epithelial cells. PG - F1689-95 LID - 10.1152/ajprenal.90333.2008 [doi] AB - 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. FAU - Breggia, A C AU - Breggia AC AD - Division of Nephrology and Transplantation, Maine Medical Center, 22 Bramhall St., Portland, ME 04102, USA. FAU - Wojchowski, D M AU - Wojchowski DM FAU - Himmelfarb, J AU - Himmelfarb J LA - eng GR - P20 RR018789/RR/NCRR NIH HHS/United States PT - Journal Article DEP - 20080924 PL - United States TA - Am J Physiol Renal Physiol JT - American journal of physiology. Renal physiology JID - 100901990 RN - 0 (Actins) RN - 0 (STAT5 Transcription Factor) RN - 11096-26-7 (Erythropoietin) RN - EC 2.7.10.2 (Jak2 protein, mouse) RN - EC 2.7.10.2 (Janus Kinase 2) SB - IM MH - Actins/genetics MH - Animals MH - Cell Culture Techniques MH - Epithelial Cells/drug effects/*physiology MH - Erythropoietin/*pharmacology MH - Ischemia/*prevention & control MH - Janus Kinase 2/antagonists & inhibitors/*physiology MH - Kidney Tubules/cytology/drug effects/*physiology MH - Mice MH - Mice, Inbred C57BL MH - STAT5 Transcription Factor/*physiology MH - Signal Transduction/*physiology PMC - PMC2753302 EDAT- 2008/09/26 09:00 MHDA- 2009/03/13 09:00 PMCR- 2008/09/24 CRDT- 2008/09/26 09:00 PHST- 2008/09/26 09:00 [pubmed] PHST- 2009/03/13 09:00 [medline] PHST- 2008/09/26 09:00 [entrez] PHST- 2008/09/24 00:00 [pmc-release] AID - 90333.2008 [pii] AID - F-90333-2008 [pii] AID - 10.1152/ajprenal.90333.2008 [doi] PST - ppublish SO - Am J Physiol Renal Physiol. 2008 Dec;295(6):F1689-95. doi: 10.1152/ajprenal.90333.2008. Epub 2008 Sep 24.