演題詳細

一般口演 / Oral Session

一般口演 1 (Oral Session 1) :鉄代謝 (Iron Metabolism)

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日程
2013年10月11日(金)
時間
09:30 - 10:30
会場
第3会場 / Room No.3 (さっぽろ芸文館 3F 蓬莱)
座長・司会
川端 浩 (Hiroshi Kawabata):1
1:京都大学 血液・腫瘍内科学
 
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Regulation of hepcidin transcription by K-7174

演題番号 : OS-1-4

池田 喬司 (Takashi Ikeda):1、藤原 亨 (Toru Fujiwara):1,2、長坂 悠生 (Yuki Nagasaka):1、井上 あい (Ai Inoue):1、沖津 庸子 (Yoko Okitsu):1、勝岡 優奈 (Yuuna Katsuoka):1、福原 規子 (Noriko Fukuhara):1、大西 康 (Yasushi Onishi):1、石澤 賢一 (Kenichi Ishizawa):1,3、一迫 玲 (Ryo Ichinohasama):4、張替 秀郎 (Hideo Harigae):1,2

1:Dept. Hematology and Rheumatology, Tohoku Univ., Japan、2:Molecular Hematology/Oncology, Tohoku Univ., Japan、3:Clin. Res., Innovation and Education Center, Tohoku Univ. Hospital, Japan、4:Hematopathology, Tohoku Univ., Japan

 

(Background) Hepcidin (HAMP) is the principal iron regulatory hormone, controlling the systemic absorption and remobilization of iron from intracellular stores. The expression of HAMP increased in patients with anemia of chronic disease (ACD). Previously, a synthesized compound K-7174 was identified through chemical screening as a novel inhibitor for the adhision of monocytes to cytokine-stimulated endothelial cells. Interstingly, K-7174 restored anemia induced by inflammatory cytokines in mice (FASEB J 2003), implying that K-7174 might modulate hepcidin level. Here, we assessed the impact of K-7174 on hepcidin expression. (Method) The HepG2 hematoma cells were treated with K-7174 at a dose 20 uM for 24 h. For in vivo analysis, ICR mice were injected with K-7174 intraperitoneally. (Results) We first demonstrated that K-7174 treatment in HepG2 cells significantly decreased HAMP expression. Therefore, microarray analysis was conducted to reveal the molecular mechanism by which K-7174 inhibits the HAMP expression. We found that K-7174 induced GDF15, a negative regulator of HAMP expression, suggesting that K-7174-mediated induction of GDF15 participates in the inhibition of HAMP expression.In vivo analysis revealed that liver sample from K-7174-treated mice demonstrated significant upregulation of Gdf15 and downregulation of Hamp. Furthermore, serum hepcidin concentration was also significantly decreased in K-7174-treated mice. (Conclusion) K-7174 inhibits hepcidin expression partly by inducing GDF15. K-7174 might be considered as a potential therapeutic option to treat ACD.

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