title: Down-Regulation of Cardiac Erythropoietin Receptor and its Downstream Activated Signal Transducer Phospho-STAT-5 in a Rat Model of Chronic Kidney Disease.
abstract: BACKGROUND
  Chronic kidney disease (CKD) is often accompanied by impairment of cardiac function that may lead to major cardiac events. Erythropoietin (EPO), a kidney-produced protein, was shown to be beneficial to heart function. It was suggested that reduced EPO secretion in CKD may play a role in the initiation of heart damage.
  
  
  OBJECTIVE
  To investigate molecular changes in the EPO/ erythropoietin receptor (EPO-R) axis in rat cardiomyocytes using a rat model for CKD.
  
  
  METHODS
  We established a rat model for CKD by kidney resection. Cardiac tissue sections were stained with Masson's trichrome to assess interstitial fibrosis indicating cardiac damage. To evaluate changes in the EPO/EPO-R signaling cascade in the myocardium we measured cardiac EPO and EPO-R as well as the phosphorylation levels of STAT-5, a downstream element in this cascade.
  
  
  RESULTS
  At 11 weeks after resection, animals presented severe renal failure reflected by reduced creatinine clearance, elevated blood urea nitrogen and presence of anemia. Histological analysis revealed enhanced fibrosis in cardiac sections of CKD animals compared to the sham controls. Parallel to these changes, we found that although cardiac EPO levels were similar in both groups, the expression of EPO-R and the activated form of its downstream protein STAT-5 were significantly lower in CKD animals.
  
  
  CONCLUSIONS
  CKD results in molecular changes in the EPO/EPO-R axis. These changes may play a role in early cardiac damage observed in the cardiorenal syndrome.
authors.forename: Einat
authors.initials: E
authors.lastname: Hertzberg-Bigelman
authors.forename: Rami
authors.initials: R
authors.lastname: Barashi
authors.forename: Ran
authors.initials: R
authors.lastname: Levy
authors.forename: Lena
authors.initials: L
authors.lastname: Cohen
authors.forename: Jeremy
authors.initials: J
authors.lastname: Ben-Shoshan
authors.forename: Gad
authors.initials: G
authors.lastname: Keren
authors.forename: Michal
authors.initials: M
authors.lastname: Entin-Meer
mesh_terms: D000740:Anemia / Q000209:etiology / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D015536:Down-Regulation; D004921:Erythropoietin / Q000378:metabolism*; D005355:Fibrosis; D007677:Kidney Function Tests / Q000379:methods; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D017467:Receptors, Erythropoietin; D050799:STAT5 Transcription Factor; C000599851:erythropoietin, rat; D004921:Erythropoietin