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ID 117268
Author
Muto, Hisanori Nagoya University
Ito, Takanori Nagoya University
Tanaka, Taku Nagoya University
Yokoyama, Shinya Nagoya University
Yamamoto, Kenta Nagoya University
Imai, Norihiro Nagoya University
Ishizu, Yoji Nagoya University
Maeda, Keiko Nagoya University
Honda, Takashi Nagoya University
Ishikawa, Tetsuya Nagoya University
Kato, Asuka Nagoya University
Ohshiro, Taichi Nagoya University
Sakai, Kiyoshi Nagoya University
Hibi, Hideharu Nagoya University
Ishigami, Masatoshi Nagoya University
Fujishiro, Mitsuhiro Nagoya University
Content Type
Journal Article
Description
Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α, Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes.
Journal Title
Scientific Reports
ISSN
20452322
Publisher
Springer Nature
Volume
11
Start Page
18778
Published Date
2021-09-21
Rights
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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language
eng
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departments
Oral Sciences