Mature hepatocytes actively divide and express gamma-glutamyl transpeptidase after D-galactosamine liver injury.
OBJECTIVE
We studied the fate of hepatocytes in the rat liver after D-galactosamine injury by genetic labeling using recombinant retroviruses carrying the Escherichia coli lacZ gene coupled to a nuclear localization signal.


METHODS
Hepatocytes were either labeled by direct injection of 2.5 ml high-titer retrovirus-containing medium in the regenerating liver parenchyma after administration of a single dose of D-galactosamine. Alternatively hepatocytes were pre-labeled, 24 h after a two-thirds hepatectomy, by injecting the same volume of retroviral solution in the portal vein and D-galactosamine was administered 15 days later. Gamma-glutamyl transpeptidase and beta-galactosidase activities were assessed on cryostat sections, along with localization of the hepatocyte-specific HES6 antigen.


RESULTS
Morphological observations, as well as beta-galactosidase activity detection, showed that hepatocytes actively divide as early as 1 day after D-galactosamine injection. Gamma-glutamyl transpeptidase activity was detected in biliary cells, but also in mature hepatocytes, pre-labeled with beta-galactosidase before D-galactosamine administration.


CONCLUSIONS
These experiments demonstrate that hepatocytes can divide to restore the liver mass after D-galactosamine liver injury. Furthermore, we also show that gamma-glutamyl transpeptidase, which has been reported to be expressed only by fetal or preneoplastic hepatocytes, can be re-expressed by mature hepatocytes during the recovery process.
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Laboratoire de Transfert de Gènes, INSERM, Centre Eugène Marquis, Rennes, France.
Ferry
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D000818:Animals; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000201:enzymology* / Q000473:pathology; D005688:Galactosamine / Q000633:toxicity*; D018014:Gene Transfer Techniques; D005819:Genetic Markers; D005822:Genetic Vectors; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012190:Retroviridae / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D001616:beta-Galactosidase / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D005819:Genetic Markers; D005688:Galactosamine; D005723:gamma-Glutamyltransferase; D001616:beta-Galactosidase