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Histochemistry and Cell Biology

, Volume 130, Issue 5, pp 1005–1014 | Cite as

Triiodothyronine accelerates differentiation of rat liver progenitor cells into hepatocytes

  • Viktória László
  • Katalin Dezső
  • Kornélia Baghy
  • Veronika Papp
  • Ilona Kovalszky
  • Géza Sáfrány
  • Snorri S. Thorgeirsson
  • Peter NagyEmail author
  • Sándor Paku
Original Paper

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.

Keywords

Oval cell Maturation Regeneration Retroviral transduction Primary mitogen 

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

Notes

Acknowledgments

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

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Viktória László
    • 1
  • Katalin Dezső
    • 1
  • Kornélia Baghy
    • 1
  • Veronika Papp
    • 1
  • Ilona Kovalszky
    • 1
  • Géza Sáfrány
    • 2
  • Snorri S. Thorgeirsson
    • 3
  • Peter Nagy
    • 1
    Email author
  • Sándor Paku
    • 1
  1. 1.First Department of Pathology and Experimental Cancer ResearchSemmelweis UniversityBudapestHungary
  2. 2.National Research Institute for Radiobiology and RadiohygieneBudapestHungary
  3. 3.Laboratory of Experimental Carcinogenesis, Center for Cancer ResearchNational Cancer Institute, National Institutes of HealthBethesdaUSA

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