title: Early detection of cysteine rich protein 61 (CYR61, CCN1) in urine following renal ischemic reperfusion injury.
abstract: BACKGROUND
  Acute renal failure (ARF) has a high morbidity and mortality. Many therapies have worked in animals but were unsuccessful in clinical trials. The inability to diagnose ARF early may have impaired the success of these trials.
  
  
  METHODS
  We screened a subtraction library to search for potential disease markers that would be induced rapidly after renal injury. Mice and rats were subjected to 30 to 40 minutes of bilateral ischemia.
  
  
  RESULTS
  mRNA for Cyr61, a secreted growth factor-inducible immediate early gene, was markedly up-regulated at two hours in the kidney but not other organs following renal ischemia. In situ hybridization studies suggested Cyr61 was synthesized in the proximal straight tubule. Cyr61 protein was analyzed by capture with heparin beads followed by Western blotting. Induction of Cyr61 protein could be detected in the kidney within one hour, peaked at four to eight hours, and remained elevated for at least 24 hours following ischemia. Cyr61 protein was detected in urine at three to six hours and peaked at six to nine hours after renal injury. Cyr61 was not detected after volume depletion, which is often difficult to differentiate from ARF.
  
  
  CONCLUSIONS
  The secreted, cysteine-rich, heparin binding protein Cyr61 is rapidly induced in proximal straight tubules following renal ischemia, and excreted in the urine where it might serve as an early biomarker of renal injury.
authors.affiliation: Renal Diagnostic and Therapeutic Unit, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Yasunari
authors.initials: Y
authors.lastname: Muramatsu
authors.forename: Michiko
authors.initials: M
authors.lastname: Tsujie
authors.forename: Yukimasa
authors.initials: Y
authors.lastname: Kohda
authors.forename: Bertha
authors.initials: B
authors.lastname: Pham
authors.forename: Alan O
authors.initials: AO
authors.lastname: Perantoni
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Sang-Kyung
authors.initials: SK
authors.lastname: Jo
authors.forename: Peter S T
authors.initials: PS
authors.lastname: Yuen
authors.forename: Leonard
authors.initials: L
authors.lastname: Craig
authors.forename: Xuzhen
authors.initials: X
authors.lastname: Hu
authors.forename: Robert A
authors.initials: RA
authors.lastname: Star
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology / Q000652:urine*; D000818:Animals; D015415:Biomarkers; D055515:Cysteine-Rich Protein 61; D015870:Gene Expression; D017874:Immediate-Early Proteins / Q000235:genetics* / Q000652:urine*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000652:urine*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology / Q000652:urine*; D014511:Uremia / Q000503:physiopathology / Q000652:urine
chemical_list: D015415:Biomarkers; C491850:CCN1 protein, mouse; C501849:CCN1 protein, rat; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger