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NAFLD exacerbates cholangitis and promotes cholangiocellular carcinoma in mice
Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition, affecting up to 25% of the population worldwide. NAFLD has been linked to several conditions, including hepatic inflammation, fibrosis, and hepatocellular carcinoma (HCC), however the role of NAFLD in cholangitis and the d...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019203/ https://www.ncbi.nlm.nih.gov/pubmed/33506599 http://dx.doi.org/10.1111/cas.14828 |
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author | Maeda, Shin Hikiba, Yohko Fujiwara, Hiroaki Ikenoue, Tsuneo Sue, Soichiro Sugimori, Makoto Matsubayashi, Mao Kaneko, Hiroaki Irie, Kuniyasu Sasaki, Tomohiko Chuma, Makoto |
author_facet | Maeda, Shin Hikiba, Yohko Fujiwara, Hiroaki Ikenoue, Tsuneo Sue, Soichiro Sugimori, Makoto Matsubayashi, Mao Kaneko, Hiroaki Irie, Kuniyasu Sasaki, Tomohiko Chuma, Makoto |
author_sort | Maeda, Shin |
collection | PubMed |
description | Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition, affecting up to 25% of the population worldwide. NAFLD has been linked to several conditions, including hepatic inflammation, fibrosis, and hepatocellular carcinoma (HCC), however the role of NAFLD in cholangitis and the development of cholangiocellular carcinoma (CCC) remains poorly understood. This study investigated whether a high‐fat diet (HFD) promotes cholangitis and the development of CCC in mice. We used liver‐specific E‐cadherin gene (CDH1) knockout mice, CDH1(∆Liv), which develop spontaneous inflammation in the portal areas along with periductal onion skin‐like fibrosis, similar to that of primary sclerosing cholangitis (PSC). An HFD or normal diet (ND) was fed to CDH1(∆Liv) mice for 7 mo. In addition, CDH1(∆Liv) mice were crossed with LSL‐Kras(G12D) mice, fed an HFD, and assessed in terms of liver tumor development. The extent of cholangitis and number of bile ductules significantly increased in mice fed an HFD compared with ND‐administered CDH1(∆Liv) mice. The numbers of Sox9 and CD44‐positive stem cell‐like cells were significantly increased in HFD mice. LSL‐Kras(G12D) /CDH1(∆Liv) HFD mice exhibited increased aggressiveness along with the development of numerous HCC and CCC, whereas LSL‐Kras(G12D)/CDH1(∆Liv) ND mice showed several macroscopic tumors with both HCC and CCC components. In conclusion, NAFLD exacerbates cholangitis and promotes the development of both HCC and CCC in mice. |
format | Online Article Text |
id | pubmed-8019203 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80192032021-04-08 NAFLD exacerbates cholangitis and promotes cholangiocellular carcinoma in mice Maeda, Shin Hikiba, Yohko Fujiwara, Hiroaki Ikenoue, Tsuneo Sue, Soichiro Sugimori, Makoto Matsubayashi, Mao Kaneko, Hiroaki Irie, Kuniyasu Sasaki, Tomohiko Chuma, Makoto Cancer Sci Original Articles Nonalcoholic fatty liver disease (NAFLD) is an increasingly common condition, affecting up to 25% of the population worldwide. NAFLD has been linked to several conditions, including hepatic inflammation, fibrosis, and hepatocellular carcinoma (HCC), however the role of NAFLD in cholangitis and the development of cholangiocellular carcinoma (CCC) remains poorly understood. This study investigated whether a high‐fat diet (HFD) promotes cholangitis and the development of CCC in mice. We used liver‐specific E‐cadherin gene (CDH1) knockout mice, CDH1(∆Liv), which develop spontaneous inflammation in the portal areas along with periductal onion skin‐like fibrosis, similar to that of primary sclerosing cholangitis (PSC). An HFD or normal diet (ND) was fed to CDH1(∆Liv) mice for 7 mo. In addition, CDH1(∆Liv) mice were crossed with LSL‐Kras(G12D) mice, fed an HFD, and assessed in terms of liver tumor development. The extent of cholangitis and number of bile ductules significantly increased in mice fed an HFD compared with ND‐administered CDH1(∆Liv) mice. The numbers of Sox9 and CD44‐positive stem cell‐like cells were significantly increased in HFD mice. LSL‐Kras(G12D) /CDH1(∆Liv) HFD mice exhibited increased aggressiveness along with the development of numerous HCC and CCC, whereas LSL‐Kras(G12D)/CDH1(∆Liv) ND mice showed several macroscopic tumors with both HCC and CCC components. In conclusion, NAFLD exacerbates cholangitis and promotes the development of both HCC and CCC in mice. John Wiley and Sons Inc. 2021-02-14 2021-04 /pmc/articles/PMC8019203/ /pubmed/33506599 http://dx.doi.org/10.1111/cas.14828 Text en © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Maeda, Shin Hikiba, Yohko Fujiwara, Hiroaki Ikenoue, Tsuneo Sue, Soichiro Sugimori, Makoto Matsubayashi, Mao Kaneko, Hiroaki Irie, Kuniyasu Sasaki, Tomohiko Chuma, Makoto NAFLD exacerbates cholangitis and promotes cholangiocellular carcinoma in mice |
title | NAFLD exacerbates cholangitis and promotes cholangiocellular carcinoma in mice |
title_full | NAFLD exacerbates cholangitis and promotes cholangiocellular carcinoma in mice |
title_fullStr | NAFLD exacerbates cholangitis and promotes cholangiocellular carcinoma in mice |
title_full_unstemmed | NAFLD exacerbates cholangitis and promotes cholangiocellular carcinoma in mice |
title_short | NAFLD exacerbates cholangitis and promotes cholangiocellular carcinoma in mice |
title_sort | nafld exacerbates cholangitis and promotes cholangiocellular carcinoma in mice |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019203/ https://www.ncbi.nlm.nih.gov/pubmed/33506599 http://dx.doi.org/10.1111/cas.14828 |
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