Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia-reperfusion

E J Sharples, N Patel, P Brown, K Stewart, H Mota-Philipe, M Sheaff, J Kieswich, D Allen, S Harwood, M Raftery, C Thiemermann, M M Yaqoob

Research output: Contribution to journalArticle

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Abstract

Erythropoietin (EPO) is upregulated by hypoxia and causes proliferation and differentiation of erythroid progenitors in the bone marrow through inhibition of apoptosis. EPO receptors are expressed in many tissues, including the kidney. Here it is shown that a single systemic administration of EPO either preischemia or just before reperfusion prevents ischemia-reperfusion injury in the rat kidney. Specifically, EPO (300 U/kg) reduced cylomerular dysfunction and tubular injury (biochemical and histologic assessment) and prevented C, caspase-3, -8, and -9 activation in vivo and reduced apoptotic cell death. In human (HK-2) proximal tubule epithelial cells, EPO attenuated cell death in response to oxidative stress and serum starvation. EPO reduced DNA fragmentation and prevented caspase-3 activation, with upregulation of Bcl-X-L and XIAP. The antiapoptotic effects of EPO were dependent oil JAK2 signaling and the phosphorylation of Akt by phosphatidylinositol 3-kinase. These findings may have major implications in the treatment of acute renal tubular damage.

Original languageEnglish
Pages (from-to)2115-2124
Number of pages10
JournalJournal of the American Society of Nephrology
Volume15
DOIs
Publication statusPublished - 2004

Keywords

  • GENE-EXPRESSION
  • MOUSE KIDNEY
  • RAT-KIDNEY
  • KAPPA-B
  • APOPTOSIS
  • NECROSIS
  • CELLS
  • INDUCTION
  • ISCHEMIA/REPERFUSION
  • CASPASES

Cite this

Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia-reperfusion. / Sharples, E J ; Patel, N ; Brown, P ; Stewart, K ; Mota-Philipe, H ; Sheaff, M ; Kieswich, J ; Allen, D ; Harwood, S ; Raftery, M ; Thiemermann, C ; Yaqoob, M M .

In: Journal of the American Society of Nephrology, Vol. 15, 2004, p. 2115-2124.

Research output: Contribution to journalArticle

Sharples, EJ, Patel, N, Brown, P, Stewart, K, Mota-Philipe, H, Sheaff, M, Kieswich, J, Allen, D, Harwood, S, Raftery, M, Thiemermann, C & Yaqoob, MM 2004, 'Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia-reperfusion', Journal of the American Society of Nephrology, vol. 15, pp. 2115-2124. https://doi.org/10.1097/01.ASN.0000135059.67385.5D
Sharples, E J ; Patel, N ; Brown, P ; Stewart, K ; Mota-Philipe, H ; Sheaff, M ; Kieswich, J ; Allen, D ; Harwood, S ; Raftery, M ; Thiemermann, C ; Yaqoob, M M . / Erythropoietin protects the kidney against the injury and dysfunction caused by ischemia-reperfusion. In: Journal of the American Society of Nephrology. 2004 ; Vol. 15. pp. 2115-2124.
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AU - Kieswich, J

AU - Allen, D

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AU - Raftery, M

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AB - Erythropoietin (EPO) is upregulated by hypoxia and causes proliferation and differentiation of erythroid progenitors in the bone marrow through inhibition of apoptosis. EPO receptors are expressed in many tissues, including the kidney. Here it is shown that a single systemic administration of EPO either preischemia or just before reperfusion prevents ischemia-reperfusion injury in the rat kidney. Specifically, EPO (300 U/kg) reduced cylomerular dysfunction and tubular injury (biochemical and histologic assessment) and prevented C, caspase-3, -8, and -9 activation in vivo and reduced apoptotic cell death. In human (HK-2) proximal tubule epithelial cells, EPO attenuated cell death in response to oxidative stress and serum starvation. EPO reduced DNA fragmentation and prevented caspase-3 activation, with upregulation of Bcl-X-L and XIAP. The antiapoptotic effects of EPO were dependent oil JAK2 signaling and the phosphorylation of Akt by phosphatidylinositol 3-kinase. These findings may have major implications in the treatment of acute renal tubular damage.

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KW - CELLS

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