title: Rapid modulation of liver-specific transcription factors after injury.
abstract: BACKGROUND
  The reaction to injury is a well-orchestrated physiologic response involving the coordinated actions of multiple integrated systems. It initially occurs at the molecular level and involves changes in gene transcription. We hypothesized that the molecular mechanisms regulating the generation of an inflammatory response are similar to those orchestrating developmental and tissue-specific expression of proteins and, in the case of the acute phase response, occur through manipulation of liver-specific transcription factors and their binding activity.
  
  
  METHODS
  Female BALB/c mice, 7 to 8 weeks old, were subjected to a 15% body surface area burn. Total and polyadenylated liver RNA was isolated, and Northern blot analysis was performed to determine the kinetics of the acute phase proteins albumin and fibrinogen and the liver-specific transcriptional factors CCAAT-enhancer binding protein (C/EBP) alpha, hepatocyte nuclear factor (HNF)-1 alpha, and HNF-4.
  
  
  RESULTS
  Induction of the injury response was shown by an increase in fibrinogen messenger RNA levels and a decrease in albumin mRNA levels. The liver-specific transcription factor C/EBP alpha decreased after injury and remained significantly lower than control at 3 hours. HNF-4 mRNA levels fell more slowly, reaching significantly lower levels at 6 hours and remaining suppressed at 34 hours. HNF-1 alpha showed the most rapid fall in mRNA levels at 30 minutes after injury and remained significantly below control levels at 34 hours.
  
  
  CONCLUSIONS
  The minimal burn injury model leads to the molecular induction of the acute phase response and induces significant and rapid changes in the liver-specific transcription factors C/EBP alpha, HNF-1 alpha, and HNF-4. These changes may represent a mechanism through which the organ-specific response to injury is mediated.
authors.affiliation: Department of Surgery, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02215.
authors.forename: P A
authors.initials: PA
authors.lastname: Burke
authors.forename: M
authors.initials: M
authors.lastname: Drotar
authors.forename: M
authors.initials: M
authors.lastname: Luo
authors.forename: M
authors.initials: M
authors.lastname: Yaffe
authors.forename: R A
authors.initials: RA
authors.lastname: Forse
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002056:Burns / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D005260:Female; D005340:Fibrinogen / Q000235:genetics; D005786:Gene Expression Regulation; D051537:Hepatocyte Nuclear Factor 1; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051557:Hepatocyte Nuclear Factor 4; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009687:Nuclear Proteins; D009928:Organ Specificity; D010750:Phosphoproteins; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C083058:C-EPB transcription factor; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; C496488:Hnf1a protein, mouse; C496496:Hnf1b protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; C501970:Tcfl4 protein, mouse; D014157:Transcription Factors; D051537:Hepatocyte Nuclear Factor 1; D051539:Hepatocyte Nuclear Factor 1-beta; D005340:Fibrinogen