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Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice

Male Tsumura-Suzuki Obese Diabetes (TSOD) mice, a spontaneous metabolic syndrome model, develop non-alcoholic steatohepatitis and liver tumors by feeding on a standard mouse diet. Nearly 70% of liver tumors express glutamine synthetase (GS), a marker of hepatocellular carcinoma. In contrast, approxi...

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Autores principales: Shao, Wenhua, Jargalsaikhan, Orgil, Ichimura-Shimizu, Mayuko, Cai, Qinyi, Ogawa, Hirohisa, Miyakami, Yuko, Atsumi, Kengo, Tomita, Mitsuru, Sutoh, Mitsuko, Toyohara, Shunji, Hokao, Ryoji, Kudo, Yasusei, Oya, Takeshi, Tsuneyama, Koichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570293/
https://www.ncbi.nlm.nih.gov/pubmed/36233225
http://dx.doi.org/10.3390/ijms231911923
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author Shao, Wenhua
Jargalsaikhan, Orgil
Ichimura-Shimizu, Mayuko
Cai, Qinyi
Ogawa, Hirohisa
Miyakami, Yuko
Atsumi, Kengo
Tomita, Mitsuru
Sutoh, Mitsuko
Toyohara, Shunji
Hokao, Ryoji
Kudo, Yasusei
Oya, Takeshi
Tsuneyama, Koichi
author_facet Shao, Wenhua
Jargalsaikhan, Orgil
Ichimura-Shimizu, Mayuko
Cai, Qinyi
Ogawa, Hirohisa
Miyakami, Yuko
Atsumi, Kengo
Tomita, Mitsuru
Sutoh, Mitsuko
Toyohara, Shunji
Hokao, Ryoji
Kudo, Yasusei
Oya, Takeshi
Tsuneyama, Koichi
author_sort Shao, Wenhua
collection PubMed
description Male Tsumura-Suzuki Obese Diabetes (TSOD) mice, a spontaneous metabolic syndrome model, develop non-alcoholic steatohepatitis and liver tumors by feeding on a standard mouse diet. Nearly 70% of liver tumors express glutamine synthetase (GS), a marker of hepatocellular carcinoma. In contrast, approximately 30% are GS-negative without prominent nuclear or structural atypia. In this study, we examined the characteristics of the GS-negative tumors of TSOD mice. Twenty male TSOD mice were sacrificed at 40 weeks and a total of 21 tumors were analyzed by HE staining and immunostaining of GS, liver fatty acid-binding protein (L-FABP), serum amyloid A (SAA), and beta-catenin. With immunostaining for GS, six (29%) tumors were negative. Based on the histological and immunohistological characteristics, six GS-negative tumors were classified into several subtypes of human hepatocellular adenoma (HCA). One large tumor showed generally similar findings to inflammatory HCA, but contained small atypical foci with GS staining and partial nuclear beta-catenin expression suggesting malignant transformation. GS-negative tumors of TSOD mice contained features similar to various subtypes of HCA. Different HCA subtypes occurring in the same liver have been reported in humans; however, the diversity of patient backgrounds limits the ability to conduct a detailed, multifaceted analysis. TSOD mice may share similar mechanisms of HCA development as in humans. It is timely to review the pathogenesis of HCA from both genetic and environmental perspectives, and it is expected that TSOD mice will make further contributions in this regard.
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spelling pubmed-95702932022-10-17 Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice Shao, Wenhua Jargalsaikhan, Orgil Ichimura-Shimizu, Mayuko Cai, Qinyi Ogawa, Hirohisa Miyakami, Yuko Atsumi, Kengo Tomita, Mitsuru Sutoh, Mitsuko Toyohara, Shunji Hokao, Ryoji Kudo, Yasusei Oya, Takeshi Tsuneyama, Koichi Int J Mol Sci Article Male Tsumura-Suzuki Obese Diabetes (TSOD) mice, a spontaneous metabolic syndrome model, develop non-alcoholic steatohepatitis and liver tumors by feeding on a standard mouse diet. Nearly 70% of liver tumors express glutamine synthetase (GS), a marker of hepatocellular carcinoma. In contrast, approximately 30% are GS-negative without prominent nuclear or structural atypia. In this study, we examined the characteristics of the GS-negative tumors of TSOD mice. Twenty male TSOD mice were sacrificed at 40 weeks and a total of 21 tumors were analyzed by HE staining and immunostaining of GS, liver fatty acid-binding protein (L-FABP), serum amyloid A (SAA), and beta-catenin. With immunostaining for GS, six (29%) tumors were negative. Based on the histological and immunohistological characteristics, six GS-negative tumors were classified into several subtypes of human hepatocellular adenoma (HCA). One large tumor showed generally similar findings to inflammatory HCA, but contained small atypical foci with GS staining and partial nuclear beta-catenin expression suggesting malignant transformation. GS-negative tumors of TSOD mice contained features similar to various subtypes of HCA. Different HCA subtypes occurring in the same liver have been reported in humans; however, the diversity of patient backgrounds limits the ability to conduct a detailed, multifaceted analysis. TSOD mice may share similar mechanisms of HCA development as in humans. It is timely to review the pathogenesis of HCA from both genetic and environmental perspectives, and it is expected that TSOD mice will make further contributions in this regard. MDPI 2022-10-07 /pmc/articles/PMC9570293/ /pubmed/36233225 http://dx.doi.org/10.3390/ijms231911923 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shao, Wenhua
Jargalsaikhan, Orgil
Ichimura-Shimizu, Mayuko
Cai, Qinyi
Ogawa, Hirohisa
Miyakami, Yuko
Atsumi, Kengo
Tomita, Mitsuru
Sutoh, Mitsuko
Toyohara, Shunji
Hokao, Ryoji
Kudo, Yasusei
Oya, Takeshi
Tsuneyama, Koichi
Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice
title Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice
title_full Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice
title_fullStr Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice
title_full_unstemmed Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice
title_short Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice
title_sort spontaneous occurrence of various types of hepatocellular adenoma in the livers of metabolic syndrome-associated steatohepatitis model tsod mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9570293/
https://www.ncbi.nlm.nih.gov/pubmed/36233225
http://dx.doi.org/10.3390/ijms231911923
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