Temporal and spatial patterns of transin/stromelysin RNA expression following toxic injury in rat liver.
We have examined the expression of the extracellular matrix-degrading metalloprotease transin/stromelysin during the early phases of rat liver regeneration following toxic injury by a single dose of carbon tetrachloride (CCl4). In situ hybridization displayed cell type-specific spatial and temporal RNA expression patterns with high transcript levels in small proportions of hepatocytes and non-parenchymal cells, peaking at 24 and 48 h after intoxication, respectively. In agreement with the presence of c-fos and c-jun recognition sites on the transin gene, expression of these oncogenes preceded transin expression. Transin-expressing hepatocytes were largely localized in areas subsequently eliminated by necrosis due to CCl4 intoxication. As a consequence of these expression patterns and the key function of transin as an activator of interstitial collagenase, it seems that the hepatic fibrosis observed after CCl4 administration may be related to fibrogenesis unbalanced by fibrolysis due to altered transin expression.
Institute of Pathology, Klinikum Steglitz, Free University of Berlin, Federal Republic of Germany.
H
H
Herbst
O
O
Heinrichs
D
D
Schuppan
S
S
Milani
H
H
Stein
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004790:Enzyme Induction; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics; D009336:Necrosis; D009693:Nucleic Acid Hybridization; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000502:physiology; D015347:RNA Probes; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014158:Transcription, Genetic
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D015347:RNA Probes; D012333:RNA, Messenger; D002251:Carbon Tetrachloride; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3