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Title: Pivotal role of liver sinusoidal endothelial cells in NAFLD/NASH progression.
Authors: Miyao, Masashi  kyouindb  KAKEN_id
Kotani, Hirokazu  kyouindb  KAKEN_id
Ishida, Tokiko
Kawai, Chihiro
Manabe, Sho
Abiru, Hitoshi
Tamaki, Keiji  kyouindb  KAKEN_id
Author's alias: 小谷, 泰一
Issue Date: Oct-2015
Publisher: Nature Publishing Group
Journal title: Laboratory investigation
Volume: 95
Issue: 10
Start page: 1130
End page: 1144
Abstract: Liver sinusoidal endothelial cells (LSECs) are involved in the transport of nutrients, lipids, and lipoproteins, and LSEC injury occurs in various liver diseases including nonalcoholic fatty liver disease (NAFLD). However, the association between LSEC injury and NAFLD progression remains elusive. Accordingly, in this study, we aimed to elucidate the precise role of LSEC in the pathophysiology of NAFLD using two different mouse models, namely the choline-deficient, L-amino acid-defined and high-fat diet models. Administration of these diets resulted in liver metabolic dysregulation mimicking human NAFLD, such as steatosis, ballooning, lobular inflammation, and fibrosis, as well as central obesity, insulin resistance, and hyperlipidemia. LSEC injury appeared during the simple steatosis phase, and preceded the appearance of activated Kupffer cells and hepatic stellate cells (HSCs). These results indicate that LSEC injury may have a 'gatekeeper' role in the progression from simple steatosis to the early nonalcoholic steatohepatitis (NASH) stage, and LSEC injury may be necessary for the activation of Kupffer cells and HSCs, which in turn results in the development and perpetuation of chronic liver injuries. Taken together, our data provide new insights into the role of LSEC injury in NAFLD/NASH pathogenesis.
Description: Advance online publication 27 July 2015
Rights: This is the accepted manuscript of the article is available at
The full-text file will be made open to the public on 27 July 2016 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。This is not the published version. Please cite only the published version.
DOI(Published Version): 10.1038/labinvest.2015.95
PubMed ID: 26214582
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