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ID 51044
フルテキストURL
著者
Tashiro, Keitaro Yale Univ, Sch Med, Sect Digest Dis, Dept Internal Med
Satoh, Ayano Okayama Univ, Grad Sch Nat Sci
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
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)
発行日
2013-03
出版物タイトル
The American Journal of Pathology
182巻
3号
出版者
Elsevier Science Inc
開始ページ
786
終了ページ
795
ISSN
0002-9440
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1016/j.ajpath.2012.11.032
言語
English
著作権者
© 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
論文のバージョン
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DOI
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