論文

査読有り
2013年7月26日

Conditional loss of heparin-binding EGF-like growth factor results in enhanced liver fibrosis after bile duct ligation in mice

Biochemical and Biophysical Research Communications
  • Takayo Takemura
  • Yuichi Yoshida
  • Shinichi Kiso
  • Takashi Kizu
  • Kunimaro Furuta
  • Hisao Ezaki
  • Mina Hamano
  • Mayumi Egawa
  • Norihiro Chatani
  • Yoshihiro Kamada
  • Yasuharu Imai
  • Shigeki Higashiyama
  • Ryo Iwamoto
  • Eisuke Mekada
  • Tetsuo Takehara
  • 全て表示

437
2
開始ページ
185
終了ページ
191
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.bbrc.2013.05.097

Our aims were to evaluate the involvement of heparin-binding EGF-like growth factor (HB-EGF) in liver fibrogenesis of humans and mice and to elucidate the effect of HB-EGF deficiency on cholestatic liver fibrosis using conditional HB-EGF knockout (KO) mice. We first demonstrated that gene expression of HB-EGF had a positive significant correlation with that of collagen in human fibrotic livers, and was increased in bile duct ligation (BDL)-induced fibrotic livers in mouse. We then generated conditional HB-EGF knockout (KO) mice using the interferon inducible Mx-1 promoter driven Cre recombinase transgene and wild type (WT) and KO mice were subjected to BDL. After BDL, KO mice exhibited enhanced liver fibrosis with increased expression of collagen, compared with WT mice. Finally, we used mouse hepatic stellate cells (HSCs) to examine the role of HB-EGF in the activation of these cells and showed that HB-EGF antagonized TGF-β-induced gene expression of collagen in mouse primary HSCs. Interestingly, HB-EGF did not prevent the TGF-β-induced nuclear accumulation of Smad3, but did lead to stabilization of the Smad transcriptional co-repressor TG-interacting factor. In conclusion, our data suggest a possible protective role of HB-EGF in cholestatic liver fibrosis. © 2013 Elsevier Inc.

リンク情報
DOI
https://doi.org/10.1016/j.bbrc.2013.05.097
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23743191
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84880747065&origin=inward
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84880747065&origin=inward
ID情報
  • DOI : 10.1016/j.bbrc.2013.05.097
  • ISSN : 0006-291X
  • ISSN : 1090-2104
  • eISSN : 1090-2104
  • PubMed ID : 23743191
  • SCOPUS ID : 84880747065

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