title: Reperfusion stress induced during intermittent selective clamping accelerates rat liver regeneration through JNK pathway.
abstract: OBJECTIVE
  Liver resection includes temporal vascular inflow occlusion resulting in ischemia/reperfusion injury in the remnant liver. Here, we developed a rat model of selective lobe occlusion to isolate reperfusion stress from ischemia and to analyze its effect on liver regeneration.
  
  
  METHODS
  Left lateral and median lobes of liver were either mobilized or subjected twice for 10min to ischemia followed by 5min reperfusion prior to resection while the regenerative lobes were only subjected to reperfusion.
  
  
  RESULTS
  Although intermittent reperfusion stress induced higher levels of serum transaminases, analysis of cell cycle regulators revealed accelerated regenerative response compared to standard partial hepatectomy. The G0/G1 transition occurred before tissue resection, as evidenced by c-fos, junB, and IL-6 induction. Following hepatectomy, Cyclin D1 up-regulation, G1/S transition, and cell division occurred earlier than normal. Unexpectedly, liver mobilization, a component of the clamping procedure, also resulted in earlier G1/S transition. The shortened G1-phase was driven by the c-Jun N-terminal Kinase pathway and was associated with an oxidative stress response as evidenced by the expression of inducible nitric oxide synthase.
  
  
  CONCLUSIONS
  Intermittent selective clamping of lobes to be resected induced reperfusion stress on remnant liver that was beneficial for liver regeneration, suggesting this procedure could be applied in clinical practice.
authors.affiliation: Inserm U522, CHU Pontchaillou, Rue Henri Le Guilloux, Rennes, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Duval
authors.forename: Sasse-Fanie
authors.initials: SF
authors.lastname: Mbatchi
authors.forename: Stéphane
authors.initials: S
authors.lastname: Grandadam
authors.forename: Claire
authors.initials: C
authors.lastname: Legendre
authors.forename: Pascal
authors.initials: P
authors.lastname: Loyer
authors.forename: Catherine
authors.initials: C
authors.lastname: Ribault
authors.forename: Claire
authors.initials: C
authors.lastname: Piquet-Pellorce
authors.forename: Christiane
authors.initials: C
authors.lastname: Guguen-Guillouzo
authors.forename: Karim
authors.initials: K
authors.lastname: Boudjema
authors.forename: Anne
authors.initials: A
authors.lastname: Corlu
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D019938:Cyclin D1 / Q000235:genetics; D016193:G1 Phase / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006498:Hepatectomy / Q000379:methods; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology*; D016192:Resting Phase, Cell Cycle / Q000502:physiology; D016196:S Phase / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013525:Surgical Instruments; D000099156:Superoxide Dismutase 2
chemical_list: D019938:Cyclin D1; D051547:Heme Oxygenase-1; D015850:Interleukin-6; D048031:JNK Mitogen-Activated Protein Kinases; D052247:Nitric Oxide Synthase Type II; D016760:Proto-Oncogene Proteins c-fos; D050796:STAT3 Transcription Factor; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C530106:Ccnd1 protein, rat; C494088:Stat3 protein, rat; C496318:Nos2 protein, rat