Apoptotic pathway related to oval cell proliferation

Yoshihiko Yano, Yoshitake Hayashi, Tadahisa Teramoto, Miyuki Nakaji, Peter Nagy, Toshiaki Ninomiya, Atsushi Wada, Midori Hirai, Ryang Kim Soo, Yasushi Seo, Seitetsu Yoon, Masato Kasuga

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4 Citations (Scopus)


Background and Aim: Oval cells, liver stem cell-derived cells, are generated from the liver periportal region and spread into the parenchyma by an autocrine signaling pathway. The mechanism behind how oval cells take their place among packed silent hepatocytes, however, is not well understood. We hypothesized that apoptosis involves a decrease in hepatocytes surrounding oval cells. Methods: Male Fisher rats were treated using the AAF/PH protocol to induce oval cells in the liver. Apoptosis was assessed by measuring the activity of caspase-3, -8 and -9, and apoptosis-related molecules such as caspase-3, Fas, Fas-L and Bax were also assessed by immunohistochemical analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). Apoptosis was confirmed by TUNEL staining. Regarding antiapoptotic factors, nuclear factor-κB (NF-κB) DNA binding activity and proliferating cell nuclear antigen (PCNA) expression were examined. Results: NF-κB elevated at the early stage of oval cell proliferation. Conversely, caspase activity increased after NF-κB elevation. The mRNA of caspase-3, Fas, Fas-L and Bax was induced during and after AAF/PH treatment. Immunohistochemically, oval cells lacked the expression of these proteins, whereas the hepatocytes, particularly those surrounding oval cells, expressed strongly. Conclusion: The present study suggests that the apoptosis in hepatocytes through both extrinsic and intrinsic pathways mediates oval cell proliferation.

Original languageEnglish
Pages (from-to)866-872
Number of pages7
JournalJournal of Gastroenterology and Hepatology (Australia)
Issue number8
Publication statusPublished - Aug 2004



  • Apoptosis
  • Caspase
  • Fas
  • Fas-L
  • Oval cells

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Yano, Y., Hayashi, Y., Teramoto, T., Nakaji, M., Nagy, P., Ninomiya, T., Wada, A., Hirai, M., Soo, R. K., Seo, Y., Yoon, S., & Kasuga, M. (2004). Apoptotic pathway related to oval cell proliferation. Journal of Gastroenterology and Hepatology (Australia), 19(8), 866-872. https://doi.org/10.1111/j.1440-1746.2004.03431.x