title: Hepatic expression of A disintegrin and metalloproteinase (ADAM) and ADAMs with thrombospondin motives (ADAM-TS) enzymes in patients with chronic liver diseases.
abstract: OBJECTIVE
  ADAMs (A Disintegrin And Metalloprotease) are multifunctional, membrane-bound and soluble cell surface glycoproteins with numerous functions in cell physiology. We assessed the expression of ADAMs in fibrotic liver disease of different aetiologies and clarified whether the expression of ADAMs is related to histological staging of fibrosis. In addition, the expression of ADAMs was determined in different cell types of liver.
  
  
  METHODS
  Seventy-one biopsy samples from patients with chronic liver diseases were analyzed for mRNA expression of ADAM-8, -9, -12, -28, -TS1, -TS2, matrix metalloprotease (MMP)-2, -9 and tissue inhibitor of metalloproteinases-1 and -2 by quantitative real-time RT-PCR.
  
  
  RESULTS
  The ADAM expression in liver injury is independent of aetiology. A strong correlation between ADAM -9, -28, -TS1 versus MMP-2 and SMA was identified. Activated hepatic stellate cells (HSC) showed increased mRNA expression of ADAM-8, -9, -12, -28, -TS2 compared to quiescent HSC. Significant differences between histological stages of fibrosis were found for ADAM-28, MMP-2 and MMP-9.
  
  
  CONCLUSIONS
  The results suggest that ADAMs are differentially expressed in the liver. We assume that ADAM-9, -TS1 and -TS2 play a crucial role in extracellular matrix remodeling during fibrotic processes in the liver.
authors.affiliation: Institute of Clinical Chemistry, Hannover Medical School, 30623 Hannover, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Schwettmann
authors.forename: Michael
authors.initials: M
authors.lastname: Wehmeier
authors.forename: Dunja
authors.initials: D
authors.lastname: Jokovic
authors.forename: Krasimira
authors.initials: K
authors.lastname: Aleksandrova
authors.forename: Korbinian
authors.initials: K
authors.lastname: Brand
authors.forename: Michael P
authors.initials: MP
authors.lastname: Manns
authors.forename: Ralf
authors.initials: R
authors.lastname: Lichtinghagen
authors.forename: Matthias J
authors.initials: MJ
authors.lastname: Bahr
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000072199:ADAM12 Protein; D000818:Animals; D001706:Biopsy; D002478:Cells, Cultured; D055166:Hepatic Stellate Cells / Q000201:enzymology / Q000473:pathology; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019700:Thrombospondin 1 / Q000235:genetics; D019699:Thrombospondins / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics; D000099262:Thrombospondin 2
chemical_list: D051722:ADAM Proteins; D000072199:ADAM12 Protein; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D008565:Membrane Proteins; D012333:RNA, Messenger; D019700:Thrombospondin 1; D019699:Thrombospondins; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D000099262:Thrombospondin 2; C000606480:ADAM12 protein, human; C410224:ADAM28 protein, human; C068490:ADAM8 protein, human; C098339:ADAM9 protein, human