Nonalcoholic steatohepatitis and hepatocellular carcinoma in galectin-3 knockout mice

Yuko Nakanishi, Koichi Tsuneyama, Kazuhiro Nomoto, Makoto Fujimoto, Thucydides L. Salunga, Takahiko Nakajima, Shigeharu Miwa, Yoshihiro Murai, Shinichi Hayashi, Ichiro Kato, Koichi Hiraga, Daniel K. Hsu, Fu-Tong Liu, Yasuo Takano

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Aim: Nonalcoholic fatty liver disease (NAFLD) represents a growing health concern due to its rapidly increasing prevalence worldwide. Nonalcoholic steatohepatitis (NASH) is a progressing form of NAFLD, and recently many studies have reported that it could eventually develop into hepatocellular carcinoma (HCC). We previously reported that 6-month-old male galectin-3 knockout (gal3-/-) mice developed clinicopathological features similar to those of NAFLD in humans. Our aim was to investigate the changes in liver histology in gal3-/- mice by long-term observation. Methods: We initially investigated three 15-month-old gal3-/- mice, of which two developed multiple liver nodules with dysplastic changes. Then, we histopathologically examined the liver specimens of the 15-, 20- and 25-month-old gal3-/- mice and attempted to evaluate the liver morphology by contrast enhanced computed tomography (CT) before sacrifice. Results: At the age of 15 months or later, gal3-/- mice developed liver nodules with varying degrees of architectural and nuclear atypia based on mild to moderate delicate zone 3 fibrosis. In addition, we successfully confirmed the presence of some of the liver nodules by CT. We report herein that gal3-/- mice develop dysplastic liver nodules and HCC. Conclusions: We believe that it would be interesting to use this murine model to investigate liver carcinogenesis based on a natural history of NAFLD. Furthermore, CT scanning might be a useful tool for longitudinal evaluation of morphological changes in vivo.

Original languageEnglish (US)
Pages (from-to)1241-1251
Number of pages11
JournalHepatology Research
Volume38
Issue number12
DOIs
StatePublished - 2008

Keywords

  • Computed tomography
  • Galectin-3
  • Hepatocellular carcinoma
  • Nonalcoholic fatty liver disease
  • nonalcoholic steatohepatitis

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases

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    Nakanishi, Y., Tsuneyama, K., Nomoto, K., Fujimoto, M., Salunga, T. L., Nakajima, T., Miwa, S., Murai, Y., Hayashi, S., Kato, I., Hiraga, K., Hsu, D. K., Liu, F-T., & Takano, Y. (2008). Nonalcoholic steatohepatitis and hepatocellular carcinoma in galectin-3 knockout mice. Hepatology Research, 38(12), 1241-1251. https://doi.org/10.1111/j.1872-034X.2008.00395.x