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 Citations (Scopus)

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

Fingerprint

Galectin 3
Knockout Mice
Hepatocellular Carcinoma
Liver
Tomography
Non-alcoholic Fatty Liver Disease
Histology
Carcinogenesis
Fibrosis
Observation
Health

Keywords

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

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases

Cite this

Nakanishi, Y., Tsuneyama, K., Nomoto, K., Fujimoto, M., Salunga, T. L., Nakajima, 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

Nonalcoholic steatohepatitis and hepatocellular carcinoma in galectin-3 knockout mice. / Nakanishi, Yuko; Tsuneyama, Koichi; Nomoto, Kazuhiro; Fujimoto, Makoto; Salunga, Thucydides L.; Nakajima, Takahiko; Miwa, Shigeharu; Murai, Yoshihiro; Hayashi, Shinichi; Kato, Ichiro; Hiraga, Koichi; Hsu, Daniel K.; Liu, Fu-Tong; Takano, Yasuo.

In: Hepatology Research, Vol. 38, No. 12, 2008, p. 1241-1251.

Research output: Contribution to journalArticle

Nakanishi, Y, Tsuneyama, K, Nomoto, K, Fujimoto, M, Salunga, TL, Nakajima, T, Miwa, S, Murai, Y, Hayashi, S, Kato, I, Hiraga, K, Hsu, DK, Liu, F-T & Takano, Y 2008, 'Nonalcoholic steatohepatitis and hepatocellular carcinoma in galectin-3 knockout mice', Hepatology Research, vol. 38, no. 12, pp. 1241-1251. https://doi.org/10.1111/j.1872-034X.2008.00395.x
Nakanishi Y, Tsuneyama K, Nomoto K, Fujimoto M, Salunga TL, Nakajima T et al. Nonalcoholic steatohepatitis and hepatocellular carcinoma in galectin-3 knockout mice. Hepatology Research. 2008;38(12):1241-1251. https://doi.org/10.1111/j.1872-034X.2008.00395.x
Nakanishi, Yuko ; Tsuneyama, Koichi ; Nomoto, Kazuhiro ; Fujimoto, Makoto ; Salunga, Thucydides L. ; Nakajima, Takahiko ; Miwa, Shigeharu ; Murai, Yoshihiro ; Hayashi, Shinichi ; Kato, Ichiro ; Hiraga, Koichi ; Hsu, Daniel K. ; Liu, Fu-Tong ; Takano, Yasuo. / Nonalcoholic steatohepatitis and hepatocellular carcinoma in galectin-3 knockout mice. In: Hepatology Research. 2008 ; Vol. 38, No. 12. pp. 1241-1251.
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AU - Nakanishi, Yuko

AU - Tsuneyama, Koichi

AU - Nomoto, Kazuhiro

AU - Fujimoto, Makoto

AU - Salunga, Thucydides L.

AU - Nakajima, Takahiko

AU - Miwa, Shigeharu

AU - Murai, Yoshihiro

AU - Hayashi, Shinichi

AU - Kato, Ichiro

AU - Hiraga, Koichi

AU - Hsu, Daniel K.

AU - Liu, Fu-Tong

AU - Takano, Yasuo

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N2 - 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.

AB - 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.

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