title: Protein fingerprinting of the extracellular matrix remodelling in a rat model of liver fibrosis--a serological evaluation.
abstract: OBJECTIVE
  We investigated nine novel biomarkers of extracellular matrix (ECM) remodelling in a rat model of liver fibrosis.
  
  
  METHODS
  Liver fibrosis was induced in 52 male Wistar rats by inhalation of carbon tetrachloride and the level of hepatic fibrosis was assessed by Sirius red staining compared with controls. The novel serum biochemical markers assessed in the model were type I-(C1M), type III-(C3M), type IV-(C4M) and type VI-(C6M) collagen, citrullinated vimentin (VICM) and biglycan (BGM) all protein fragments generated by matrix metalloproteinases; and formation markers of type III-(P3NP), type VI (P4NP 7S) and type V (P5CP) collagen; hepatic mRNA type I collagen alpha-1 chain levels, serum potassium, sodium, osmolarity, alanine aminotransferase, lactate dehydrogenase, albumin and creatinine.
  
  
  RESULTS
  Stratification of the CCl(4) -treated rats according to total hepatic collagen showed that the degradation markers were significantly elevated in mild to severe fibrosis except for C6M which was also elevated in early fibrosis (P < 0.05). The highest Z-scores in early and moderate fibrosis were provided by P4NP 7S and alanine aminotransferase. All nine markers of ECM remodelling were highly related to the extent of liver fibrosis induced by CCl(4) . The novel collagen formation marker, P4NP 7S, was reliable for the detection of early fibrosis, while the combination of the two markers, C6M and P5CP provided the best correlation with hepatic fibrosis in all fibrosis levels.
  
  
  CONCLUSIONS
  As the markers can be used for translational science, these markers may provide valuable information for the evaluation of liver fibrosis in clinical settings.
authors.affiliation: Nordic Bioscience, Fibrosis Biology and Biomarkers, Herlev, Denmark. djl@nordicbioscience.com
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Leeming
authors.forename: Inger
authors.initials: I
authors.lastname: Byrjalsen
authors.forename: Wladimiro
authors.initials: W
authors.lastname: Jiménez
authors.forename: Claus
authors.initials: C
authors.lastname: Christiansen
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D058578:Biglycan / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D002251:Carbon Tetrachloride / Q000633:toxicity; D024042:Collagen Type I / Q000097:blood; D003404:Creatinine / Q000097:blood; D005109:Extracellular Matrix / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D016014:Linear Models; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D010449:Peptide Mapping / Q000379:methods; D011188:Potassium / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012709:Serum Albumin / Q000032:analysis; D012964:Sodium / Q000097:blood; D014746:Vimentin / Q000097:blood
chemical_list: D058578:Biglycan; D015415:Biomarkers; D024042:Collagen Type I; D012709:Serum Albumin; D014746:Vimentin; D012964:Sodium; D003404:Creatinine; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D011188:Potassium