title: Erythropoietin pretreatment ameliorates renal ischaemia-reperfusion injury by activating PI3K/Akt signalling.
abstract: OBJECTIVE
  Renal ischaemia-reperfusion (I/R) injury, a primary cause of acute renal failure, can induce high morbidity and mortality. This study aimed to explore the effect of erythropoietin on renal I/R injury and its underlying mechanism.
  
  
  METHODS
  Fifty male Sprague-Dawley rats were randomly allocated to three groups (n = 10): the sham group, the renal ischaemia-reperfusion-saline (IRI) group, and the IRI+-Erythropoietin (EPO) group. Erythropoietin (250, 500, 1000 U/kg) was intraperitoneally injected 30 min before inducing I/R. Renal I/R injury were induced by clamping the left renal artery for 30 min followed by reperfusion, along with a contralateral nephrectomy. Renal function and histological damage were determined after 24 h reperfusion. The expression of pro-inflammatory cytokines interleukin-6 (IL-6), interleukin-1 β (IL-1β), and tumour necrosis factor-α (TNF-α) in the serum and renal tissue were evaluated by enzyme linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Further, the effects of erythropoietin on PI3K/Akt signalling, erythropoietin receptor (EPOR) and nuclear factor (NF)-κB activation were measured by Western blotting.
  
  
  RESULTS
  Erythropoietin pretreatment can significantly decrease the level of renal dysfunction in a dose-dependent manner, attenuated the renal histological changes, the expression of TNF-α, IL-1β, and IL-6, the levels of reactive oxygen species (ROS) production and NF-κB p65 phosphorylation in renal tissue upon IRI. Moreover, erythropoietin pretreatment could further activate the PI3K/Akt signalling and induced EPOR activity.
  
  
  CONCLUSIONS
  Erythropoietin pretreatment could attenuate renal I/R injury by suppressing inflammation, which was associated with activating PI3K/Akt signalling though EPOR activation. Our findings suggest that erythropoietin may be a novel practical strategy to prevent renal I/R injury.
authors.affiliation: Department of Nephrology, University of Electronic Science and Technology, Sichuan Academy of Sciences & Sichuan Provincial People's Hospital, Chengdu, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Zhang
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Zou
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhong
authors.forename: Hanlu Ding Fei
authors.initials: HD
authors.lastname: Deng
authors.forename: Lei
authors.initials: L
authors.lastname: Pu
authors.forename: Kun
authors.initials: K
authors.lastname: Peng
authors.forename: Li
authors.initials: L
authors.lastname: Wang
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004921:Erythropoietin / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000819:agonists / Q000378:metabolism; D015427:Reperfusion Injury / Q000097:blood / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; C000594089:IL1B protein, rat; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D017467:Receptors, Erythropoietin; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt
keywords: PI3K/Akt; erythropoietin; renal ischaemia reperfusion injury