title: Cyclosporine or FK506 decrease mature epidermal growth factor protein expression and renal tubular regeneration in rat kidneys with ischemia/reperfusion injury.
abstract: BACKGROUND
  Epidermal growth factor (EGF) plays an important role in tubular regeneration in kidneys with ischemia/reperfusion (I/R) injury. This study was undertaken to evaluate the influence of cyclosporine A (CsA) or FK506 on mature EGF expression and tubular regeneration in rat kidneys with I/R injury.
  
  
  METHODS
  Two separate studies were performed. First, the expression of EGF and tubular regeneration was observed in rat kidneys with I/R injury on days 1, 2, 3, 5, and 7. Second, the dose-dependent response of EGF expression and tubular regeneration to CsA (5, 10, and 20 mg/kg) or FK506 (0.25, 0.5, and 1.0 mg/kg) was observed in rat kidneys with I/R injury. I/R injury was induced by clamping both renal arteries for 45 min, and CsA or FK506 was injected just after release of vascular clamps. Rats were sacrificed on day 1 for evaluation of EGF expression, and on day 2 for evaluation of BudU-positive cells. Renal function, tubular injury score, EGF expression assessed by immunoblotting, levels of CsA and FK506 in whole blood, and immunostaining for BrdU was studied.
  
  
  RESULTS
  EGF expression was maximal on day 1 (cortex, 29-fold; medulla, 31-fold compared with sham-operated controls), and renal tubular regeneration measured with the number of BrdU-positive cells was maximal on days 2 and 3 in kidney with I/R injury, and thereafter the level of EGF and the number of BrdU-positive cells decreased progressively. CsA or FK506 treatment to ischemic rat kidneys reduced the expression of EGF and the number of BrdU-positive cells in a dose-dependent manner.
  
  
  CONCLUSIONS
  CsA or FK506 treatment delays recovery from acute tubular necrosis, and this may be associated with decreased EGF expression by CsA or FK506.
authors.affiliation: Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Yang
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Lee
authors.forename: Sun Woo
authors.initials: SW
authors.lastname: Lim
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Jung
authors.forename: Wan Young
authors.initials: WY
authors.lastname: Kim
authors.forename: Hyung Wook
authors.initials: HW
authors.lastname: Kim
authors.forename: Bum Soon
authors.initials: BS
authors.lastname: Choi
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Cha
authors.forename: Yong Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Byung Kee
authors.initials: BK
authors.lastname: Bang
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D016572:Cyclosporine / Q000378:metabolism / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology*; D007684:Kidney Tubules / Q000033:anatomy & histology / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D016559:Tacrolimus / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000963:Antimetabolites; D007166:Immunosuppressive Agents; D004815:Epidermal Growth Factor; D016572:Cyclosporine; D001973:Bromodeoxyuridine; D016559:Tacrolimus