attenuated DR6 expression in endometriosis

• Project/Area Number: 26861335
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Oita University
• Principal Investigator: KAI Kentaro 大分大学, 医学部, 客員研究員 (90457622)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
• Keywords: 生殖内分泌学 / 子宮内膜症 / DR6 / エピジェネティクス / ヒストン脱アセチル化酵素阻害剤 / アポトーシス / 細胞増殖 / エピジェネティック / デスレセプター6 / ヒストン脱アセチル化酵素阻害薬

Outline of Final Research Achievements

The purpose of this study is to evaluate the involvement of death receptor (DR) 6 in the pathogenesis of endometriosis. Endometriotic cyst stromal cells (ECSCs) and normal endometrial stromal cells (NESCs) were isolated from ovarian endometriotic tissues and the eutopic endometrial tissues. The expression of DR6 mRNA and protein in ECSCs and NESCs were also examined.DR6 expression was attenuated in ECSCs and in endometriotic tissues, and its expression was upregulated by VPA stimulation. VPA treatment resulted in an accumulation of acetylated histone H4 in the promoter region of the DR6 gene. DR6 knockdown directed the stimulation of cell proliferation and the resistance to apoptosis in NESCs. The present findings suggested that DR6 is involved in the pathogenesis of endometriosis by creating the proliferative and anti-apoptotic characteristics of endometriosis.The results also suggest that histone deacetylase inhibitors are promising agents for the treatment of endometriosis.

Research Products

• [Journal Article] Enhanced miR-210 expression promotes the pathogenesis of endometriosis through activation of signal transducer and activator of transcription 3. (2015)
  • Author(s): Okamoto M, Nasu K, Abe W, Aoyagi Y, Kawano Y, Kai K, Moriyama M et al.
  • Journal Title: JOURNAL OF Human Reproduction Volume: 30 Issue: 3 Pages: 632-641
  • DOI: 10.1093/humrep/deu332
  • Peer Reviewed
• [Journal Article] Wisteria floribunda agglutinin-binding glycan expression is decreased in endometriomata. (2014)
  • Author(s): Hirakawa T, Nasu K, Kai K, Aoyagi Y, Ishii T, Uemura T, Yano M, Narahara H.
  • Journal Title: Reprod Biol Endocrinol. Volume: 12 Issue: 1 Pages: 100-100
  • DOI: 10.1186/1477-7827-12-100
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Aberrant histone modification in endometriosis. (2014)
  • Author(s): Nasu K, Kawano Y, Kai K, Aoyagi Y, Abe W, Okamoto M, Narahara H.
  • Journal Title: Front Biosci (Landmark Ed). Volume: 19 Pages: 1202-1214
  • Peer Reviewed
• [Presentation] Death Receptor 6 is Epigenetically Silenced by Histone Deacetylation in Endometriosis and Promotes the Pathogenesis of Endometriosis (2015)
  • Author(s): Kentaro Kai, Kaei Nasu, Yoko Aoyagi, Mamiko Okamoto, Hirakawa Tomoko, Hisashi Narahara
  • Organizer: IFFS/JSRM International Meeting 2015 in Yokohama
  • Place of Presentation: Pacifico Yokohama（神奈川県横浜市）
  • Year and Date: 2015-04-25
  • Int'l Joint Research
• [Presentation] Wisteria floribunda agglutinin-binding glycan expression is decreased in endometriosis (2015)
  • Author(s): Kentaro Kai, Kaei Nasu, Tomoko Hirakawa, Yoko Aoyagi, Terukazu Ishii, Tetsuya Uemura, Mitsutake Yano, Hisashi Narahara
  • Organizer: Society for Reproductive Investigation 62nd Annual Scientific Meeting
  • Place of Presentation: Hilton San Francisco Union Square, San Francisco, CA, USA
  • Year and Date: 2015-03-28
• [Presentation] DR6 is epigenetically involved in the pathogenesis of endometriosis by creating the proliferative and anti-apoptotic characteristics (2014)
  • Author(s): Kentaro Kai, Kaei Nasu, Yoko Aoyagi, Yoshiyuki Tsukamoto, Naoki Hijiya, Mamiko Okamoto, Masatsugu Moriyama, Hisashi Narahara
  • Organizer: 第29回日本生殖免疫学会
  • Place of Presentation: 文京区・伊藤国際学術研究センター
  • Year and Date: 2014-12-12 – 2014-12-13
• [Presentation] Death receptor 6 is epigenetically silenced by histone deacetylation in endometriosis (2014)
  • Author(s): Kentaro Kai, Kaei Nasu, Yoko Aoyagi, Yoshiyuki Tsukamoto, Naoki Hijiya, Mamiko Okamoto, Masatsugu Moriyama, Hisashi Narahara
  • Organizer: 第59回日本人類遺伝学会
  • Place of Presentation: 江戸川区・タワーホール船堀
  • Year and Date: 2014-11-19 – 2014-11-22
• [Presentation] Death receptor 6 is epigenetically silenced by histone deacetylation in Endometriosis and Promotes the Pathogenesis of Endometriosis (2014)
  • Author(s): Kentaro Kai, Kaei Nasu, Yoko Aoyagi, Yoshiyuki Tsukamoto, Naoki Hijiya, Mamiko Okamoto, Masatsugu Moriyama, Hisashi Narahara
  • Organizer: 3rd Asian Conference of Endometriosis
  • Place of Presentation: Songeui Medical Campus, The Catholic University of Korea, Seoul, Korea
  • Year and Date: 2014-10-24 – 2014-10-26
• [Presentation] Death receptor 6 is epigenetically silenced by histone deacetylation in endometriosis and promotes the pathogenesis of endometriosis (2014)
  • Author(s): Kentaro Kai, Kaei Nasu, Yukie Kawano, Wakana Abe, Mamiko Okamoto, Hisashi Narahara
  • Organizer: 第66回日本産科婦人科学会学術講演会
  • Place of Presentation: 千代田区・東京国際フォーラム
  • Year and Date: 2014-04-18 – 2015-04-20