ID | 51044 |
フルテキストURL | |
著者 |
Tashiro, Keitaro
Yale Univ, Sch Med, Sect Digest Dis, Dept Internal Med
Utsumi, Teruo
Yale Univ, Sch Med, Sect Digest Dis, Dept Internal Med
Chung, Chuhan
Yale Univ, Sch Med, Sect Digest Dis, Dept Internal Med
Iwakiri, Yasuko
Yale Univ, Sch Med, Sect Digest Dis, Dept Internal Med
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抄録 | Nogo-B (reticulon 4B) accentuates hepatic fibrosis and cirrhosis, but the mechanism remains unclear. The aim of this study was to identify the role of Nogo-B in hepatic stellate cell (HSC) apoptosis in cirrhotic livers. Cirrhosis was generated by carbon tetrachloride inhalation in wild-type (WT) and Nogo-A/B knockout (Nogo-B KO) mice. HSCs were isolated from WT and Nogo-B KO mice and cultured for activation and transformation to myofibroblasts (MF-HSCs). Human hepatic stellate cells (LX2 cells) were used to assess apoptotic responses of activated HSCs after silencing or overexpressing Nogo-B. Livers from cirrhotic Nogo-B KO mice showed significantly reduced fibrosis (P < 0.05) compared with WT mice. Apoptotic cells were more prominent in fibrotic areas of cirrhotic Nogo-B KO livers. Nogo-B KO MF-HSCs showed significantly increased Levels of apoptotic markers, cleaved poly (ADP-ribose) polymerase, and caspase-3 and -8 (P < 0.05) compared with WT MF-HSCs in response to staurosporine. Treatment with tunicamycin, an endoplasmic reticulum stress inducer, increased cleaved caspase-3 and -8 levels in Nogo-B KO MF-HSCs compared with WT MF-HSCs (P < 0.01). In LX2 cells, Nogo-B knockdown enhanced apoptosis in response to staurosporine, whereas Nogo-B overexpression inhibited apoptosis. The absence of Nogo-B enhances apoptosis of HSCs in experimental cirrhosis. Selective blockade of Nogo-B in HSCs may represent a potential therapeutic strategy to mitigate liver fibrosis. (Am J Pathol 2013, 182: 786-795; http://dx.doLorg/10.1016Aajpath.2012.11.032)
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発行日 | 2013-03
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出版物タイトル |
The American Journal of Pathology
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巻 | 182巻
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号 | 3号
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出版者 | Elsevier Science Inc
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開始ページ | 786
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終了ページ | 795
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ISSN | 0002-9440
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資料タイプ |
学術雑誌論文
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オフィシャル URL | http://dx.doi.org/10.1016/j.ajpath.2012.11.032
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言語 |
英語
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著作権者 | © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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論文のバージョン | author
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査読 |
有り
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DOI | |
Web of Science KeyUT |