title: A useful model to audit liver resolution from cirrhosis in rats using functional proteomics.
abstract: BACKGROUND
  We conducted a rat cirrhosis and recovery model, on the basis of which proteomics was used to audit liver resolution from cirrhosis.
  
  
  METHODS
  Micronodular cirrhosis was established using Sprague-Dawley rats fed thioacetamide, and spontaneous recovery from cirrhosis was acquired after thioacetamide withdrawal.
  
  
  RESULTS
  Over the course of a 2-, 3-, and 6-week recovery, macronodular cirrhosis, uneven liver surface, and nearly normal liver surface were acquired, respectively. Specific liver enzymes, hepatitis activity index, hepatocytes apoptosis index, number of activated Kupffer cells and hepatic stellate cells, and area of fibrosis bands consistently peaked at the end of thioacetamide administration and decreased progressively during the recovery period. mRNA expression of proinflammatory cytokines and proapoptotic molecules peaked around the end of thioacetamide administration and decreased thereafter. Using two-dimensional gel electrophoresis, the seven most upregulated and six most downregulated protein spots were analyzed by matrix-assisted laser desorption/ionization time-of-flight. Of these, GST-P2 and its isoforms, GST-alpha and GST-M, were chosen for further validation using immunohistochemistry. Expression of GST-P peaked at the 2-week recovery, whereas GST-alpha and GST-M remained at strong levels at the 6-week recovery.
  
  
  CONCLUSIONS
  The mechanism of resolution from cirrhosis can be extensively investigated using the presented model which, for example, showed GST isoforms performing their roles at different time phases.
authors.affiliation: Department of Surgery, Chang Gung Memorial Hospital, School of Traditional Chinese Medicine, Taipei, Taiwan.
authors.forename: Erh-Hao
authors.initials: EH
authors.lastname: Liu
authors.forename: Miin-Fu
authors.initials: MF
authors.lastname: Chen
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
authors.forename: Yu-Pin
authors.initials: YP
authors.lastname: Ho
authors.forename: Ren-Chin
authors.initials: RC
authors.lastname: Wu
authors.forename: Tse-Ching
authors.initials: TC
authors.lastname: Chen
authors.forename: Yi-Yin
authors.initials: YY
authors.lastname: Jan
authors.forename: Tai-Long
authors.initials: TL
authors.lastname: Pan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D005982:Glutathione Transferase / Q000032:analysis / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008969:Molecular Sequence Data; D040901:Proteomics / Q000379:methods*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013853:Thioacetamide
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D013853:Thioacetamide; D005982:Glutathione Transferase