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Tumor necrosis factor-α promotes bile ductular transdifferentiation of mature rat hepatocytes in vitro
https://asahikawa-med.repo.nii.ac.jp/records/4275
https://asahikawa-med.repo.nii.ac.jp/records/427568230489-0428-4548-9a78-b294b9bbd88b
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5017.pdf (4.4 MB)
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Item type | 学術雑誌論文 / Journal Article_02(1) | |||||||
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公開日 | 2013-02-04 | |||||||
タイトル | ||||||||
タイトル | Tumor necrosis factor-α promotes bile ductular transdifferentiation of mature rat hepatocytes in vitro | |||||||
言語 | en | |||||||
言語 | ||||||||
言語 | eng | |||||||
キーワード | ||||||||
言語 | en | |||||||
主題Scheme | Other | |||||||
主題 | Ductular reaction | |||||||
キーワード | ||||||||
言語 | en | |||||||
主題Scheme | Other | |||||||
主題 | Transdifferentiation | |||||||
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言語 | en | |||||||
主題Scheme | Other | |||||||
主題 | Tumor necrosis factor-α | |||||||
キーワード | ||||||||
言語 | en | |||||||
主題Scheme | Other | |||||||
主題 | Liver fibrosis | |||||||
キーワード | ||||||||
言語 | en | |||||||
主題Scheme | Other | |||||||
主題 | Hepatocytes | |||||||
キーワード | ||||||||
言語 | en | |||||||
主題Scheme | Other | |||||||
主題 | Bile duct cells | |||||||
キーワード | ||||||||
言語 | en | |||||||
主題Scheme | Other | |||||||
主題 | JNK-c-Jun pathway | |||||||
資源タイプ | ||||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||
資源タイプ | journal article | |||||||
著者 |
西川, 祐司
× 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
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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 | ||||||||
収録物識別子タイプ | PISSN | |||||||
収録物識別子 | 0730-2312 | |||||||
DOI | ||||||||
関連タイプ | isVersionOf | |||||||
識別子タイプ | DOI | |||||||
関連識別子 | 10.1002/jcb.24424 | |||||||
PubMed番号 | ||||||||
識別子タイプ | PMID | |||||||
関連識別子 | 23097189 | |||||||
抄録 | ||||||||
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 | ||||||||
内容記述タイプ | Other | |||||||
内容記述 | Author(preprint) | |||||||
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内容記述タイプ | Other | |||||||
内容記述 | text | |||||||
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出版タイプ | AM | |||||||
出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||||
フォーマット | ||||||||
内容記述タイプ | Other | |||||||
内容記述 | application/pdf | |||||||
ID(XooNIps) | ||||||||
値 | 23097189 | |||||||
閲覧数(XooNIps) | ||||||||
値 | 922 | |||||||
ダウンロード数(XooNIps) | ||||||||
値 | 958 |