TY - JOUR
T1 - Nonalcoholic steatohepatitis and hepatocellular carcinoma in galectin-3 knockout mice
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
PY - 2008
Y1 - 2008
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.
KW - Computed tomography
KW - Galectin-3
KW - Hepatocellular carcinoma
KW - Nonalcoholic fatty liver disease
KW - nonalcoholic steatohepatitis
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U2 - 10.1111/j.1872-034X.2008.00395.x
DO - 10.1111/j.1872-034X.2008.00395.x
M3 - Article
C2 - 18637146
AN - SCOPUS:55449125261
VL - 38
SP - 1241
EP - 1251
JO - International Hepatology Communications
JF - International Hepatology Communications
SN - 0928-4346
IS - 12
ER -