title: Injury-induced changes in liver specific transcription factors HNF-1α and HNF-4α.
abstract: BACKGROUND
  The hepatic acute phase response(APR) is an organ-specific response to a diverse array of insults and is largely under transcriptional control. Liver-specific transcription factors, hepatic nuclear factors (HNFs)-1α and 4α play important roles in maintenance of liver phenotype and function and their binding activity changes early after injury. However, their roles in modulation of the liver's response over time are not defined.
  
  
  METHODS
  C57/BL6 mice were anesthetized and exposed to 95°C water for 10 s to create a 15% body surface area full-thickness burn. At specific time points, the mice were sacrificed. An ELISA for IL-6 was performed on serum and hepatic mRNA levels for fibrinogen-γ and serum amyloid A(SAA)-3 were obtained through polymerase chain reaction (PCR). Transcriptional factor binding activity was assessed with electrophoretic mobility shift assays.
  
  
  RESULTS
  Serum IL-6 levels peaked at 3 h and fibrinogen-γ and SAA mRNA levels increased more than 6-fold at 12 h before returning to control levels at 48 h. The binding activity of HNF-4α and HNF-1α rapidly declined after injury (1.5 h) but recovered to near control level at 24 and 6 h, respectively.
  
  
  CONCLUSIONS
  Changes in HNF-4α and HNF-1α binding occurred before changes in acute phase protein mRNA levels and were preceded by the peak in IL-6 levels. The rapid suppression and reconstitution of liver-specific transcription factor binding after injury may represent a mechanism that allows the normal liver phenotype to change and an injury-response phenotype to prevail. This mechanism in the liver's adaptive response to injury suggests a central role for both HNF-4α and HNF-1α in transcriptional regulation of the hepatic APR.
authors: Department of Surgery, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors: Graciela
authors: G
authors: Bauzá
authors: Glenn
authors: G
authors: Miller
authors: Neema
authors: N
authors: Kaseje
authors: Zhongyan
authors: Z
authors: Wang
authors: Alan
authors: A
authors: Sherburne
authors: Suresh
authors: S
authors: Agarwal
authors: Peter A
authors: PA
authors: Burke
mesh_terms: D000210:Acute-Phase Reaction / Q000209:etiology* / Q000378:metabolism*; D000818:Animals; D002056:Burns / Q000150:complications*; D005340:Fibrinogen / Q000378:metabolism; D005786:Gene Expression Regulation; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000378:metabolism*; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D012333:RNA, Messenger / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism
chemical_list: D051538:Hepatocyte Nuclear Factor 1-alpha; D051557:Hepatocyte Nuclear Factor 4; C496488:Hnf1a protein, mouse; C496593:Hnf4a protein, mouse; D015850:Interleukin-6; D012333:RNA, Messenger; C076498:Saa3 protein, mouse; D000685:Serum Amyloid A Protein; D005340:Fibrinogen