STAT3 defciency prevents hepatocarcinogenesis and promotes biliary proliferation in thioacetamide-induced liver injury

Mitsuhiko Abe, Takafumi Yoshida, Jun Akiba, Yu Ikezono, Fumitaka Wada, Atsutaka Masuda, Takahiko Sakaue, Toshimitsu Tanaka, Hideki Iwamoto, Toru Nakamura, Michio Sata, Hironori Koga, Akihiko Yoshimura, Takuji Torimura

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Aim To elucidate the role of STAT3 in hepatocarcinogenesis and biliary ductular proliferation following chronic liver injury. METHODS We investigated thioacetamide (TAA)-induced liver injury, compensatory hepatocyte proliferation, and hepatocellular carcinoma (HCC) development in hepatic STAT3-deficient mice. In addition, we evaluated TAAinduced biliary ductular proliferation and analyzed the activation of sex determining region Y-box9 (SOX9) and Yes-associated protein (YAP), which regulate the transdifferentiation of hepatocytes to cholangiocytes. RESULTS Both compensatory hepatocyte proliferation and HCC formation were significantly decreased in hepatic STAT3-deficient mice as compared with control mice. STAT3 deficiency resulted in augmentation of hepatic necrosis and fbrosis. On the other hand, biliary ductular proliferation increased in hepatic STAT3-defcient livers as compared with control livers. SOX9 and YAP were upregulated in hepatic STAT3-defcient hepatocytes. CONCLUSION STAT3 may regulate hepatocyte proliferation as well as transdifferentiation into cholangiocytes and serve as a therapeutic target for HCC inhibition and biliary regeneration.

Original languageEnglish
Pages (from-to)6833-6844
Number of pages12
JournalWorld Journal of Gastroenterology
Volume23
Issue number37
DOIs
Publication statusPublished - 2017 Oct 7

Keywords

  • Ductular reaction
  • Hepatocellular carcinoma
  • Sex determining region Y-box9
  • Signal transducer and activator of transcription 3
  • Transdifferentiation
  • Yesassociated protein

ASJC Scopus subject areas

  • Gastroenterology

Fingerprint Dive into the research topics of 'STAT3 defciency prevents hepatocarcinogenesis and promotes biliary proliferation in thioacetamide-induced liver injury'. Together they form a unique fingerprint.

  • Cite this

    Abe, M., Yoshida, T., Akiba, J., Ikezono, Y., Wada, F., Masuda, A., Sakaue, T., Tanaka, T., Iwamoto, H., Nakamura, T., Sata, M., Koga, H., Yoshimura, A., & Torimura, T. (2017). STAT3 defciency prevents hepatocarcinogenesis and promotes biliary proliferation in thioacetamide-induced liver injury. World Journal of Gastroenterology, 23(37), 6833-6844. https://doi.org/10.3748/wjg.v23.i37.6833