| Item type |
学術雑誌論文 / Journal Article_02(1) |
| 公開日 |
2013-02-04 |
| タイトル |
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|
タイトル |
Tumor necrosis factor-α promotes bile ductular transdifferentiation of mature rat hepatocytes in vitro |
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言語 |
en |
| 言語 |
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|
言語 |
eng |
| キーワード |
|
|
主題Scheme |
Other |
|
キーワード |
Ductular reaction |
| キーワード |
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主題Scheme |
Other |
|
キーワード |
Transdifferentiation |
| キーワード |
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|
主題Scheme |
Other |
|
キーワード |
Tumor necrosis factor-α |
| キーワード |
|
|
主題Scheme |
Other |
|
キーワード |
Liver fibrosis |
| キーワード |
|
|
主題Scheme |
Other |
|
キーワード |
Hepatocytes |
| キーワード |
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|
主題Scheme |
Other |
|
キーワード |
Bile duct cells |
| キーワード |
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|
主題Scheme |
Other |
|
キーワード |
JNK-c-Jun pathway |
| 資源タイプ |
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|
資源タイプ |
journal article |
| 著者 |
西川, 祐司
Sone, Masayuki
Nagahama, Yasuharu
Kumagai, Eriko
Doi, Yuko
Omori, Yasufumi
Yoshioka, Toshiaki
Tokairin, Takuo
Yoshida, Masayuki
Yamamoto, Yohei
Ito, Akihiko
Sugiyama, Toshihiro
Enomoto, Katsuhiko
|
| 書誌情報 |
Journal of cellular biochemistry
巻 114,
号 4,
p. 831-843,
発行日 2013-04-01
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| ISSN |
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|
収録物識別子タイプ |
PISSN |
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収録物識別子 |
0730-2312 |
| DOI |
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関連タイプ |
isVersionOf |
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識別子タイプ |
DOI |
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関連識別子 |
10.1002/jcb.24424 |
| PubMed番号 |
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識別子タイプ |
PMID |
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関連識別子 |
23097189 |
| 抄録 |
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内容記述タイプ |
Abstract |
|
内容記述 |
We previously showed that mature hepatocytes could transdifferentiate into bile ductular cells when placed in a collagen-rich microenvironment. To explore the mechanism of transdifferentiation, we examined whether inflammatory cytokines affected the phenotype of hepatocytes in a three-dimensional culture system. Spheroidal aggregates of rat hepatocytes were embedded within a type I collagen gel matrix and cultured in the presence of various cytokines. In the control, hepatocytes gradually lost expression of albumin, tyrosine aminotransferase, and hepatocyte nuclear factor (HNF)-4α, while aberrantly expressed bile ductular markers, including cytokeratin 19 (CK 19) and spermatogenic immunoglobulin superfamily (SgIGSF). Among the cytokines examined, tumor necrosis factor (TNF)-α inhibited expression of albumin and HNF-4α, both at mRNA and protein levels. After culturing for 2 weeks with TNF-α, hepatocytic spheroids were transformed into extensively branching tubular structures composed of CK 19- and SgIGSF-positive small cuboidal cells. These cells responded to secretin with an increase in secretion and expressed functional bile duct markers. TNF-α also induced the phosphorylation of Jun N-terminal kinase (JNK) and c-Jun, and the morphogenesis was inhibited by SP600125, a specific JNK inhibitor. Furthermore, in chronic rat liver injury induced by CCl(4) , ductular reaction in the centrilobular area demonstrated strong nuclear staining of phosphorylated c-Jun. Our results demonstrate that TNF-α promotes the ductular transdifferentiation of hepatocytes and suggest a role of TNF-α in the pathogenesis of ductular reaction. |
|
言語 |
en |
| 注記 |
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|
内容記述タイプ |
Other |
|
注記 |
Author(preprint) |
| 資源タイプ |
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|
内容記述タイプ |
Other |
|
資源タイプ |
text |
| 著者版フラグ |
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|
出版タイプ |
AM |
| フォーマット |
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内容記述タイプ |
Other |
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内容記述 |
application/pdf |
| ID(XooNIps) |
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23097189 |
| 閲覧数(XooNIps) |
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| ダウンロード数(XooNIps) |
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|
958 |
5017.pdf (4.4 MB)
