[Fibrogenesis and fibrolysis in the liver].
Fibrosis, a consequence of most chronic liver diseases, may be conceived as the result of a disturbed balance between fibrogenesis and fibrolysis. We have studied several genes activated during the course of these processes in rat and human liver by immunohistology and in situ hybridization using tissue sections and cultured lipocytes. Activated lipocytes and portal fibroblasts proved to be the principal sources of extracellular matrix proteins and of the fibrogenic growth factor TGF-beta 1. The expression patterns of matrix-metalloproteinases (MMP)-1, -2, -3, and tissue inhibitors of metalloproteinases (TIMP)-1 and -2 genes suggest particularly reduced degradation of collagen type I. Increased fibrogenesis and inadequate fibrolysis may thus explain the accumulation of qualitatively altered extracellular matrix enriched in collagen type I as observed in fibrotic liver. Expression of PDGF-A by epithelial liver cells and of PDGF receptors by activated lipocytes points to paracrine regulatory loops stimulating the proliferation of cells potentially contributing to fibrosis. Continuous parenchymal damage may thus disrupt the balance between fibrogenesis and fibrolysis, resulting in fibrosis.
Herbst
H
H
Institut für Pathologie, Klinikum Benjamin Franklin, Freie Universität Berlin.
Schuppan
D
D
Milani
S
S
D017667:Adipocytes / Q000473:pathology / Q000502:physiology; D000818:Animals; D017364:Collagenases / Q000096:biosynthesis; D004848:Epithelium / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D018093:Gelatinases / Q000096:biosynthesis; D015870:Gene Expression; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D008099:Liver / Q000473:pathology* / Q000502:physiology*; D008103:Liver Cirrhosis / Q000473:pathology* / Q000503:physiopathology; D008106:Liver Cirrhosis, Experimental / Q000473:pathology* / Q000503:physiopathology; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis; D014176:Protein Biosynthesis; D051381:Rats; D019716:Tissue Inhibitor of Metalloproteinase-2; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D010982:Platelet-Derived Growth Factor; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; D019716:Tissue Inhibitor of Metalloproteinase-2; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1