title: Heat-shock pre-treatment reduces liver injury and aids liver recovery after partial hepatectomy in mice.
abstract: BACKGROUND
  Heat-shock proteins (HSPs) are members of a chaperone protein family reported to modify stress responses. The aim of this study was to clarify the hypothesis of whether pre-treatment with heat shock reduces liver damage and influences liver regeneration after partial hepatectomy.
  
  
  METHODS
  Mice (N=6) were divided into two groups: the control group underwent partial hepatectomy without heat shock pre-treatment, the heat shock (HS) group underwent partial hepatectomy 12 hours after pre-treatment with heat shock. Mice were sacrificed at different time points after hepatectomy, remnant liver and blood were collected for further analyses in blood samples and liver tissues. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin-6 (IL6), and tumor necrosis factor-alpha (TNFα) were measured using enzyme-linked immunosorbent assay (ELISA). We used tissue samples for several experiments: staining by 5-bromo-2-deoxyuridine (BrdU), evaluation of cytokines, transcription factors and signal-transduction associated proteins.
  
  
  RESULTS
  HSP70 levels in the liver were clearly increased from 6 h to 72 h after heat shock treatment. Serum ALT and AST levels were significantly reduced in the HS group compared to the control group after partial hepatectomy. Liver regeneration rate and BrdU labeling index were significantly higher in the HS group than in the control group after partial hepatectomy. IL6 and TNFα in serum and liver tissues were significantly reduced in the HS group compared to the control group after hepatectomy. We did not detect phosphorylation of signal transducer and activator of transcription-3 (STAT3) protein by western blotting. Binding activities of transcription factors: nuclear factor-interleukin-6 (NF-IL6) and nuclear factor-kappa B (NF-kB) were significantly lower in the HS group than in the control group after hepatectomy.
  
  
  CONCLUSIONS
  Pre-treatment with heat shock appears to reduce liver injury and promote liver regeneration, as HSP70 can reduce the inflammatory response and up-regulate liver regeneration without IL6 STAT signaling pathway in the liver after partial hepatectomy.
authors.affiliation: Department of Surgery, School of Medicine, Kurume University, Fukuoka, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Oka
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Akagi
authors.forename: Tetsushi
authors.initials: T
authors.lastname: Kinugasa
authors.forename: Nobuya
authors.initials: N
authors.lastname: Ishibashi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Iwakuma
authors.forename: Ichitarou
authors.initials: I
authors.lastname: Shiratsuchi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Shirouzu
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006498:Hepatectomy; D006979:Hyperthermia, Induced; D018836:Inflammation Mediators; D015850:Interleukin-6 / Q000378:metabolism; D008099:Liver / Q000254:growth & development* / Q000293:injuries / Q000378:metabolism; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D018836:Inflammation Mediators; D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Heat-shock protein; heat-shock pre-treatment; hepatectomy; liver regeneration; mouse model