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A porcine placental extract prevents steatohepatitis by suppressing activation of macrophages and stellate cells in mice

Nonalcoholic fatty liver disease (NAFLD) is caused by ectopic fat accumulation in the liver. NAFLD is associated with hepatic inflammation and oxidative stress, resulting in nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Placental extracts have been used to treat various chronic disease...

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Autores principales: Xu, Liang, Nagata, Naoto, Nagashimada, Mayumi, Zhuge, Fen, Ni, Yinhua, Chen, Guanliang, Kamei, Junzo, Ishikawa, Hiroki, Komatsu, Yasuhiko, Kaneko, Shuichi, Ota, Tsuguhito
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871096/
https://www.ncbi.nlm.nih.gov/pubmed/29599925
http://dx.doi.org/10.18632/oncotarget.24587
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author Xu, Liang
Nagata, Naoto
Nagashimada, Mayumi
Zhuge, Fen
Ni, Yinhua
Chen, Guanliang
Kamei, Junzo
Ishikawa, Hiroki
Komatsu, Yasuhiko
Kaneko, Shuichi
Ota, Tsuguhito
author_facet Xu, Liang
Nagata, Naoto
Nagashimada, Mayumi
Zhuge, Fen
Ni, Yinhua
Chen, Guanliang
Kamei, Junzo
Ishikawa, Hiroki
Komatsu, Yasuhiko
Kaneko, Shuichi
Ota, Tsuguhito
author_sort Xu, Liang
collection PubMed
description Nonalcoholic fatty liver disease (NAFLD) is caused by ectopic fat accumulation in the liver. NAFLD is associated with hepatic inflammation and oxidative stress, resulting in nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Placental extracts have been used to treat various chronic diseases due to their antioxidative effect. However, the effects of the extracts on the development of NASH have yet to be elucidated. Here, we demonstrated that supplementation with an oral porcine placental extract (PPE) attenuated lipid accumulation and peroxidation, insulin resistance, inflammatory and stress signaling, and fibrogenesis in the liver of NASH model mice fed a high-cholesterol and high-fat diet. The PPE reduced the number of M1-like liver macrophages, but increased the number of anti-inflammatory M2-like macrophages, resulting in a predominance of M2 over M1 macrophage populations in the liver of NASH mice. Accordingly, the PPE suppressed lipopolysaccharide-induced M1 polarization in isolated murine peritoneal macrophages, whereas it facilitated interleukin 4-induced M2 polarization. Furthermore, the PPE reduced the hepatic stellate cell (HSC) activation associated with the attenuated transforming growth factor-β/Smad3 signaling, both in the liver of NASH mice and in RI-T cells, a HSC line. The PPE may be a potential approach to prevent NASH by limiting lipid peroxidation, promoting M2 macrophage polarization, and attenuating HSC activation.
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spelling pubmed-58710962018-03-29 A porcine placental extract prevents steatohepatitis by suppressing activation of macrophages and stellate cells in mice Xu, Liang Nagata, Naoto Nagashimada, Mayumi Zhuge, Fen Ni, Yinhua Chen, Guanliang Kamei, Junzo Ishikawa, Hiroki Komatsu, Yasuhiko Kaneko, Shuichi Ota, Tsuguhito Oncotarget Research Paper Nonalcoholic fatty liver disease (NAFLD) is caused by ectopic fat accumulation in the liver. NAFLD is associated with hepatic inflammation and oxidative stress, resulting in nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Placental extracts have been used to treat various chronic diseases due to their antioxidative effect. However, the effects of the extracts on the development of NASH have yet to be elucidated. Here, we demonstrated that supplementation with an oral porcine placental extract (PPE) attenuated lipid accumulation and peroxidation, insulin resistance, inflammatory and stress signaling, and fibrogenesis in the liver of NASH model mice fed a high-cholesterol and high-fat diet. The PPE reduced the number of M1-like liver macrophages, but increased the number of anti-inflammatory M2-like macrophages, resulting in a predominance of M2 over M1 macrophage populations in the liver of NASH mice. Accordingly, the PPE suppressed lipopolysaccharide-induced M1 polarization in isolated murine peritoneal macrophages, whereas it facilitated interleukin 4-induced M2 polarization. Furthermore, the PPE reduced the hepatic stellate cell (HSC) activation associated with the attenuated transforming growth factor-β/Smad3 signaling, both in the liver of NASH mice and in RI-T cells, a HSC line. The PPE may be a potential approach to prevent NASH by limiting lipid peroxidation, promoting M2 macrophage polarization, and attenuating HSC activation. Impact Journals LLC 2018-02-27 /pmc/articles/PMC5871096/ /pubmed/29599925 http://dx.doi.org/10.18632/oncotarget.24587 Text en Copyright: © 2018 Xu et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Xu, Liang
Nagata, Naoto
Nagashimada, Mayumi
Zhuge, Fen
Ni, Yinhua
Chen, Guanliang
Kamei, Junzo
Ishikawa, Hiroki
Komatsu, Yasuhiko
Kaneko, Shuichi
Ota, Tsuguhito
A porcine placental extract prevents steatohepatitis by suppressing activation of macrophages and stellate cells in mice
title A porcine placental extract prevents steatohepatitis by suppressing activation of macrophages and stellate cells in mice
title_full A porcine placental extract prevents steatohepatitis by suppressing activation of macrophages and stellate cells in mice
title_fullStr A porcine placental extract prevents steatohepatitis by suppressing activation of macrophages and stellate cells in mice
title_full_unstemmed A porcine placental extract prevents steatohepatitis by suppressing activation of macrophages and stellate cells in mice
title_short A porcine placental extract prevents steatohepatitis by suppressing activation of macrophages and stellate cells in mice
title_sort porcine placental extract prevents steatohepatitis by suppressing activation of macrophages and stellate cells in mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5871096/
https://www.ncbi.nlm.nih.gov/pubmed/29599925
http://dx.doi.org/10.18632/oncotarget.24587
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