Placental extract ameliorates liver fibrosis in a methionine- and choline-deficient diet-induced mouse model of non-alcoholic steatohepatitis
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- YAMAUCHI Akihiro
- Research Institute, Japan Bio Products Co., Ltd.
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- TONE Takahiro
- Research Institute, Japan Bio Products Co., Ltd.
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- TOLEDO Andreia de
- Research Institute, Japan Bio Products Co., Ltd.
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- IGARASHI Kyoko
- Research Institute, Japan Bio Products Co., Ltd.
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- SUGIMOTO Koji
- Research Institute, Japan Bio Products Co., Ltd.
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- MIYAI Haruka
- Research Institute, Japan Bio Products Co., Ltd.
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- DENG Dawei
- Research Institute, Japan Bio Products Co., Ltd.
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- NAKAMURA Junichi
- Research Institute, Japan Bio Products Co., Ltd.
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- LIM Hong Seok
- Japan Bio Products Co., Ltd.
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- KAKU Taiichi
- Japan Bio Products Co., Ltd.
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- HIRANO Eiichi
- Research Institute, Japan Bio Products Co., Ltd.
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- SHINDO Takayuki
- Department of Cardiovascular Research, Shinshu University School of Medicine
抄録
<p>Non-alcoholic steatohepatitis (NASH) is a severe form of fatty liver disease that is defined by the presence of inflammation and fibrosis, which ultimately leads to cirrhosis and hepatocellular carcinoma. We previously showed that human placental extract (hPE) was intramuscularly injected to ameliorates liver injury in a methionine- and choline-deficient (MCD) diet-induced NASH model. In the present study, we investigated the effects of hPE using dB/dB mice which exhibit obesity and insulin resistance and are thought to reproduce the pathological background of NASH. The MCD-diet induced liver atrophy accompanied by fibrosis around the liver sinusoids. hPE dose-dependently reduced the perivascular fibrosis. Moreover, αSMA-positive activated hepatic stellate cells increased in number in mice on the MCD diet, with this effect reversed by hPE treatment. hPE significantly decreased expression of Acta2, Col1a1, and Tgfb1 genes in hepatic stellate cells, and inhibited Smad phosphorylation. Moreover, hPE treatment increased the expression of the anti-oxidative genes Hmox1, Nqo1, Cat, and Sod1, and significantly enhanced nuclear factor erythroid 2-related factor 2 activity. Furthermore, hPE decreased the expression of Nox4 and attenuated the levels of intracellular reactive oxygen species. These results, along with our previous study, suggest that hPE effectively ameliorates liver fibrosis in NASH. This beneficial effect may, in part, be due to suppression of hepatic stellate cell activation.</p>
収録刊行物
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- Biomedical Research
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Biomedical Research 41 (1), 1-12, 2020-02-01
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