2-Acetylaminofluorene Dose-Dependent Differentiation of Rat Oval Cells into Hepatocytes: Confocal and Electron Microscopic Studies

S. Paku, P. Nagy, L. Kópper, Snorri S. Thorgeirsson

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Abstract

The 2-acetylaminofluorene (AAF)/partial hepatectonly (PH) model is one ofthe most extensively studied experimental systems for oval cell proliferation and differentiation. We have previously described the oval cells as forming ductular structures surrounded by basement membrane, representing extensions of the canals of Hering. Herein we analyze the differentiation of oval cells into hepatocytes after varying degrees of liver damage induced by AAF. At a low dose of AAF, most oval cells synchronously differentiate into small hepatocytes by 6 days after the PH, resulting in complete restoration of the liver structure in 10 days. Higher doses of AAF delay the differentiation process and the new hepatocytes form foci, in contrast to what is observed at the low dose. Qualitatively, the differentiation process seems to be identical at the cellular level under both conditions. The transition from the expanding oval cell population into hepatocytes was correlated with the upregulation of hepatocyte nuclear factor 4 and the disappearance of the basement membrane. Also, the differentiation of oval cells into hepatocytes coincided with the loss of alpha-fetoprotein and OV-6 staining, and the replacement of the biliary cell-specific α6 integrin and connexin 43 with the hepatocyte-specific α1 integrin and connexin 32. In addition, bile canaliculi form between the new hepatocytes. In conclusion, these results indicate the rate of oval cell differentiation into hepatocytes is context dependent and suggest that, under favorable conditions, oval cells can complete this process much faster than previously appreciated.

Original languageEnglish
Pages (from-to)1353-1361
Number of pages9
JournalHepatology
Volume39
Issue number5
DOIs
Publication statusPublished - May 2004

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2-Acetylaminofluorene
Hepatocytes
Electrons
Cell Differentiation
Basement Membrane
Integrins
Hepatocyte Nuclear Factor 4
Bile Canaliculi
Connexin 43
Liver
alpha-Fetoproteins
Up-Regulation
Cell Proliferation
Staining and Labeling

ASJC Scopus subject areas

  • Hepatology

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2-Acetylaminofluorene Dose-Dependent Differentiation of Rat Oval Cells into Hepatocytes : Confocal and Electron Microscopic Studies. / Paku, S.; Nagy, P.; Kópper, L.; Thorgeirsson, Snorri S.

In: Hepatology, Vol. 39, No. 5, 05.2004, p. 1353-1361.

Research output: Contribution to journalArticle

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