Zonal expression of hepatocytic marker enzymes during liver repopulation.
Hepatocytes are metabolically specialised cells displaying distinctive gene expression patterns within the liver lobule. Here, we investigate whether pre-cultured adult rat hepatocytes adopt periportal and pericentral enzyme expression following their transplantation into the regenerating rat liver. Isolated primary rat hepatocytes, representing a mixture of both periportal and pericentral origin, lost expression of carbamoyl phosphate synthetase I (CPS I) and cytochrome P450 subtype 2B1 (CYP2B1) in culture as shown by immunofluorescence and Western blot analysis. Accordingly, urea synthesis and CYP2B1 enzyme activity decreased. Hepatocytes from DPPIV (CD26) wild type rats were cultured for 4 and 7 days, and then transplanted into the livers of CD26 deficient rats following prior treatment with retrorsine and partial hepatectomy to drive selective donor cell proliferation. CD26 positive donor cells engrafted in the periportal regions and grew in clusters expanding into the parenchyma as time proceeded. Ten weeks after transplantation, cells derived from donors surrounding the portal veins expressed CPS I, but not CYP2B1. The reverse was true for CD26 positive cells in close proximity to the central veins displaying immunoreactivity to CYP2B1, but no longer to CPS I. Hepatocytes lose their specific marker enzyme expression in culture. After transplantation, donor hepatocytes proliferate in the host parenchyma whilst acquiring the position-specific enzyme expression of the surrounding periportal and pericentral host hepatocytes. These results indicate the high degree of plasticity of gene expression in hepatocytes subjected to a change in microenvironment.
Koenig
Sarah
S
Department of General Surgery, Faculty of Medicine and University Hospital, Georg-August-University Goettingen, 37099, Goettingen, Germany. sarah.koenig@medizin.uni-goettingen.de
Aurich
Hendryk
H
Schneider
Christian
C
Krause
Petra
P
Haftendorn
Regine
R
Becker
Heinz
H
Christ
Bruno
B
D000818:Animals; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000235:genetics / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000235:genetics / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005819:Genetic Markers; D022781:Hepatocytes / Q000201:enzymology* / Q000378:metabolism / Q000637:transplantation*; D008099:Liver / Q000166:cytology; D008115:Liver Regeneration; D051381:Rats; D011916:Rats, Inbred F344
D005819:Genetic Markers; D019362:Cytochrome P-450 CYP2B1; D002222:Carbamoyl-Phosphate Synthase (Ammonia)