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Triiodothyronine accelerates differentiation of rat liver progenitor cells into hepatocytes

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Abstract

The 2-acetaminofluorene/partial hepatectomy (AAF/Phx) model is widely used to induce oval/progenitor cell proliferation in the rat liver. We have used this model to study the impact of a primary hepatocyte mitogen, triiodothyronine (T3) on the liver regenerating by the recruitment of oval/progenitor cells. Administration of T3 transiently accelerates the proliferation of the oval cells, which is followed by rapid differentiation into small hepatocytes. The oval cell origin of the small hepatocytes has been proven by tracing retrovirally transduced and BrdU marked oval cells. The differentiating oval cells become positive for hepatocyte nuclear factor-4 and start to express hepatocyte specific connexin 32, α1 integrin, Prox1, cytochrom P450s, and form CD 26 positive bile canaliculi. At the same time oval cell specific OV-6 and alpha-fetoprotein expression is lost. The upregulation of hepatocyte specific mRNAs: albumin, tyrosine aminotransferase and tryptophan 2,3-dioxygenase detected by real-time PCR also proves hepatocytic maturation. The hepatocytic conversion of oval cells occurs on the seventh day after the Phx in this model while the first small hepatocytes appear 5 days later without T3 treatment. The administration of the primary hepatocyte mitogen T3 accelerates the differentiation of hepatic progenitor cells into hepatocytes in vivo, and that may have therapeutic potential.

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Abbreviations

AAF:

2-Acetaminofluorene

BrdU:

Bromodeoxyuridine

HNF-4:

Hepatocyte nuclear factor 4

Phx:

Partial hepatectomy

T3:

Triiodothyronine

AFP:

Alpha-fetoprotein

TAT:

Tyrosine aminotransferase

TO2:

Tryptophan 2,3-dioxygenase

Cx:

Connexin

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Acknowledgments

The authors would like to thank Sándor Spisák for helping in microdissection.

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Authors and Affiliations

  1. First Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllõi út 26, 1085, Budapest, Hungary

    Viktória László, Katalin Dezső, Kornélia Baghy, Veronika Papp, Ilona Kovalszky, Peter Nagy & Sándor Paku

  2. National Research Institute for Radiobiology and Radiohygiene, Budapest, Hungary

    Géza Sáfrány

  3. Laboratory of Experimental Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Snorri S. Thorgeirsson

Authors
  1. Viktória László
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  2. Katalin Dezső
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  3. Kornélia Baghy
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  4. Veronika Papp
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  5. Ilona Kovalszky
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  6. Géza Sáfrány
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  7. Snorri S. Thorgeirsson
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  8. Peter Nagy
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  9. Sándor Paku
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Corresponding author

Correspondence to Peter Nagy.

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Supported by OTKA T 42674 and ETT 32/2006.

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László, V., Dezső, K., Baghy, K. et al. Triiodothyronine accelerates differentiation of rat liver progenitor cells into hepatocytes. Histochem Cell Biol 130, 1005–1014 (2008). https://doi.org/10.1007/s00418-008-0482-z

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  • DOI: https://doi.org/10.1007/s00418-008-0482-z

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