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タイトル: | Pivotal role of liver sinusoidal endothelial cells in NAFLD/NASH progression. |
著者: | Miyao, Masashi Kotani, Hirokazu Ishida, Tokiko Kawai, Chihiro Manabe, Sho Abiru, Hitoshi Tamaki, Keiji |
著者名の別形: | 小谷, 泰一 |
発行日: | Oct-2015 |
出版者: | Nature Publishing Group |
誌名: | Laboratory investigation |
巻: | 95 |
号: | 10 |
開始ページ: | 1130 |
終了ページ: | 1144 |
抄録: | 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. |
記述: | Advance online publication 27 July 2015 |
著作権等: | This is the accepted manuscript of the article is available at http://dx.doi.org/10.1038/labinvest.2015.95. 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. |
URI: | http://hdl.handle.net/2433/202772 |
DOI(出版社版): | 10.1038/labinvest.2015.95 |
PubMed ID: | 26214582 |
出現コレクション: | 学術雑誌掲載論文等 |
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