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Endoreplication and polyploidy in primary culture of rat hepatic stellate cells

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Abstract

Hepatic stellate cells (HSCs), the pericytes of hepatic sinusoids, and liver myofibroblasts (rMFs), cells located in the portal field and around the pericentral area, are the principal fibrogenic cell types of the liver. In cases of liver damage HSCs undergo "activation," i.e., they acquire a myofibroblast-like appearance and synthesize huge amounts of extracellular matrix proteins (ECMs). Their proliferation ability, however, is a matter of debate. In fact, during culture the number of rat HSCs decreases, while DNA synthesis activity and DNA content per cell increase (4±0.6 times). Together with the decrease in cell number (60±19% at day 6 of primary culture compared to day 3), cell volume increases and many HSCs become multinuclear. On the other hand, in cultures of rMFs, cell number increases along with DNA synthesis, and these cells do not become multinuclear. "Activated" HSCs produce higher levels of cyclin D1 and E1 transcripts than rMFs, which correlates with their increased levels of phosphorylated retinoblastoma (Rb) protein. In activated HSCs DNA synthesis seems to be associated with polyploidy and increase in cell volume, while DNA synthesis is followed by mitosis in rMFs.

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Acknowledgements

The authors are grateful for the excellent technical help of Anke Herbst and Sandra Georgi, and the proofreading of Anthony Gardner.

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Authors and Affiliations

  1. Department of Internal Medicine, Section of Gastroenterology and Endocrinology, Georg-August University Göttingen, Robert-Koch Strasse 40, 37075, Göttingen, Germany

    Jozsef Dudas, Bernhard Saile, Hamudi El-Armouche, Isabella Aprigliano & Giuliano Ramadori

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  1. Jozsef Dudas
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  2. Bernhard Saile
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  3. Hamudi El-Armouche
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  4. Isabella Aprigliano
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  5. Giuliano Ramadori
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Correspondence to Giuliano Ramadori.

Additional information

This work was supported by the Deutsche Forschungsgemeinschaft SFB 402, project C6

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Dudas, J., Saile, B., El-Armouche, H. et al. Endoreplication and polyploidy in primary culture of rat hepatic stellate cells. Cell Tissue Res 313, 301–311 (2003). https://doi.org/10.1007/s00441-003-0768-3

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  • DOI: https://doi.org/10.1007/s00441-003-0768-3

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