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Recovery of mature hepatocytic phenotype following bile ductular transdifferentiation of rat hepatocytes in vitro

https://asahikawa-med.repo.nii.ac.jp/records/4274
https://asahikawa-med.repo.nii.ac.jp/records/4274
bb39c944-4926-4bed-963a-11eef6726fdc
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5016.pdf 5016.pdf (1.7 MB)
Item type 学術雑誌論文 / Journal Article_02(1)
公開日 2013-02-04
タイトル
タイトル Recovery of mature hepatocytic phenotype following bile ductular transdifferentiation of rat hepatocytes in vitro
言語 en
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言語 eng
資源タイプ
資源タイプ journal article
著者 Sone, Masayuki

× Sone, Masayuki

en Sone, Masayuki

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Nishikawa, Yuji

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en Nishikawa, Yuji

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Nagahama, Yasuharu

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en Nagahama, Yasuharu

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Kumagai, Eriko

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en Kumagai, Eriko

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Doi, Yuko

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en Doi, Yuko

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Omori, Yasufumi

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en Omori, Yasufumi

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Yoshioka, Toshiaki

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en Yoshioka, Toshiaki

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Tokairin, Takuo

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en Tokairin, Takuo

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Yoshida, Masayuki

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Sugiyama, Toshihiro

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Enomoto, Katsuhiko

× Enomoto, Katsuhiko

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書誌情報 The American journal of pathology

巻 181, 号 6, p. 2094-2104, 発行日 2012-12-01
ISSN
収録物識別子タイプ PISSN
収録物識別子 0002-9440
DOI
関連タイプ isVersionOf
識別子タイプ DOI
関連識別子 10.1016/j.ajpath.2012.08.034
抄録
内容記述タイプ Abstract
内容記述 We previously demonstrated that mature rat hepatocytes transdifferentiate to bile ductular cells when cultured in a three-dimensional collagen-rich matrix. Here, we show that the phenotype of transdifferentiated hepatocytes can be reversed by modulating culture conditions. Spheroidal aggregates of hepatocytes were cultured within a collagen gel matrix in the presence of serum and tumor necrosis factor-α. Spheroids transformed into ductular structures composed of small cuboidal cells, lost the expression of hepatocytic markers, whereas aberrantly expressed bile ductular markers. The transdifferentiated cells were then retrieved from the gels, plated on surfaces coated with a basement membrane-like material, and cultured in serum-free media. Cells spontaneously formed spheroidal aggregates and recovered hepatocytic phenotype. Dexamethasone (Dex), which suppressed the phosphorylation of ERK and Jun N-terminal kinase, facilitated the recovery, and the combination with interleukin-6 or oncostatin M resulted in the recovery of hepatocyte nuclear factor 4 α protein expression and the typical hepatocytic morphology, and a decrease in the expression of bile ductular markers. A cDNA microarray analysis revealed that the hepatocyte-specific mRNA expression profile was recovered in these cells. Our results demonstrate that hepatocytes are able to recover their phenotypes following bile ductular transdifferentiation, suggesting that hepatocytic and bile ductular phenotypes may be mutually reversible.
言語 en
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