2015年10月
Pivotal role of liver sinusoidal endothelial cells in NAFLD/NASH progression
LABORATORY INVESTIGATION
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- 巻
- 95
- 号
- 10
- 開始ページ
- 1130
- 終了ページ
- 1144
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/labinvest.2015.95
- 出版者・発行元
- NATURE PUBLISHING GROUP
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.
- リンク情報
- ID情報
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- DOI : 10.1038/labinvest.2015.95
- ISSN : 0023-6837
- eISSN : 1530-0307
- PubMed ID : 26214582
- Web of Science ID : WOS:000361909200004