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Analysis of the epigenetic influence especially HDAC in keloid formation

Research Project

Project/Area Number 18K08271
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionNagasaki University

Principal Investigator

KUWATSUKA Yutaka  長崎大学, 病院(医学系), 講師 (90437864)

Co-Investigator(Kenkyū-buntansha) 岩永 聰  長崎大学, 医歯薬学総合研究科(医学系), 助教 (00621947)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsケロイド / HDAC阻害剤 / エピジェネティクス
Outline of Final Research Achievements

We examined the gene expressions of extracellular matrix and transcription factors in keloid cells with HDAC inhibitor in vitro. Previously, we found HDAC2 was upregulated in the keloid tisuue, therefore, we choose Mocetinostat, Apicidin and CAY10683 which are selective HDAC2 inhibitor. As a result, any HDAC inhibitors could inhibit the COL1A2 mRNA expressions, especially mocetinostat could inhibit TGF-β1 greater extent. Moreover, higher gene expressions were detected in the MMP-1,3. These suggests mocetinostat control several transcriptional factors and improve keloid fibrosis in the keloid. More number of the studies and further mechanism examination would be needed.

Academic Significance and Societal Importance of the Research Achievements

今回の検討により、HDAC2を選択的に阻害する薬剤は、ケロイドの過剰な膠原線維産生などを抑制する可能性が見いだされた。今回検討した、ApicidinやMocetinostatなどは既に他疾患領域で内服薬として治験が行われており、安全性や使用法などが確立されつつある。さらなる検証を加え、より安全かつ低侵襲な治療法に応用可能な薬剤の開発に寄与してゆきたい。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (27 results)

All 2019 2018

All Journal Article (11 results) (of which Peer Reviewed: 8 results,  Open Access: 2 results) Presentation (16 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results)

  • [Journal Article] Involvement of Periostin in Skin Function and the Pathogenesis of Skin Diseases2019

    • Author(s)
      Kuwatsuka Yutaka、Murota Hiroyuki
    • Journal Title

      Adv Exp Med Biol

      Volume: 1132 Pages: 89-98

    • DOI

      10.1007/978-981-13-6657-4_10

    • ISBN
      9789811366567, 9789811366574
    • Related Report
      2019 Research-status Report
  • [Journal Article] Clinical and histopathological significance of PD-1 expression in cutaneous lesions of adult T-cell leukemia?lymphoma2019

    • Author(s)
      Higuchi Maho、Kuwatsuka Yutaka、Murota Hiroyuki、Iwanaga Masako、Niino Daisuke
    • Journal Title

      Pathology - Research and Practice

      Volume: 215 Issue: 1 Pages: 40-49

    • DOI

      10.1016/j.prp.2018.10.001

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Coexistence of keloids and pilomatricoma in a patient with Rubinstein-Taybi syndrome.2018

    • Author(s)
      Yagi Y, Kuwatsuka Y, Asai M, Honda M, Utani A
    • Journal Title

      Dermatol Online J

      Volume: 24 Pages: 1-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Patients with axillary Paget's disease should be carefully screened for other sites affected by the disease2018

    • Author(s)
      Fukuchi R, Kuwatsuka Y, Koike Y, Sato Y, Nishimoto K, Utani A
    • Journal Title

      Eur J Dermatol

      Volume: 28 Pages: 83-84

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epithelial-mesenchymal transition in Bowen's disease when arising de novo and acquiring invasive capacity2018

    • Author(s)
      Koike Yuta、Yozaki Mariko、Kuwatsuka Yutaka、Utani Atsushi
    • Journal Title

      The Journal of Dermatology

      Volume: 45 Issue: 6 Pages: 748-750

    • DOI

      10.1111/1346-8138.14290

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Bullous pemphigoid induced by ipilimumab in a patient with metastatic malignant melanoma after unsuccessful treatment with nivolumab2018

    • Author(s)
      Kuwatsuka Yutaka、Iwanaga Akira、Kuwatsuka Sayaka、Okubo Yumi、Murayama Naoya、Ishii Norito、Hashimoto Takashi、Utani Atsushi
    • Journal Title

      The Journal of Dermatology

      Volume: 45 Issue: 1

    • DOI

      10.1111/1346-8138.14043

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Diffuse alveolar hemorrhage with pseudoprogression during nivolumab therapy in a patient with malignant melanoma2018

    • Author(s)
      Ikeda Takaya、Yamaguchi Hiroyuki、Dotsu Yosuke、Taniguchi Hirokazu、Gyoutoku Hiroshi、Senju Hiroaki、Sakamoto Noriho、Iwanaga Satoshi、Kuwatsuka Yutaka、Fukuda Minoru、Mukae Hiroshi
    • Journal Title

      Thoracic Cancer

      Volume: 9 Issue: 11 Pages: 1522-1524

    • DOI

      10.1111/1759-7714.12872

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 下肢にDiffuse Large B-cell Lymphomaを生じ、Epstein-Barr Virus再活性化の関与が疑われたメトトレキサート関連リンパ増殖性疾患の1例2018

    • Author(s)
      村山直也, 小池雄太, 田崎典子, 鍬塚大, 富村沙織, 竹中基, 宇谷厚志
    • Journal Title

      西日本皮膚科

      Volume: 80 Pages: 214-218

    • NAID

      130007503566

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 皮膚有棘細胞癌が合併した抗TIF1-γ抗体陽性皮膚筋炎の1例2018

    • Author(s)
      福地麗雅, 鍬塚さやか, 佐藤之恵, 鍬塚大, 宇谷厚志
    • Journal Title

      西日本皮膚科

      Volume: 80 Pages: 331-335

    • NAID

      130007503563

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 【皮膚付属器腫瘍】 背部に生じたMalignant Spiradenomaの1例2018

    • Author(s)
      吉見公佑, 鍬塚大, 小池雄太, 富村沙織, 橋迫美貴子, 木下直江, 福岡順也, 宇谷厚志
    • Journal Title

      皮膚科の臨床

      Volume: 80 Pages: 1049-1053

    • Related Report
      2018 Research-status Report
  • [Journal Article] Pseudoxanthoma elasticum-like papillary dermal elastolysis 8例の検討. Pseudoxanthoma elasticumとの相違点を中心に2018

    • Author(s)
      岩永聰, 鍬塚大, 大久保佑美, 小池雄太, 宿輪哲生, 鳥山史, 赤星吉徳, 穐山雄一郎, 今福武, 宇谷厚志
    • Journal Title

      皮膚科の臨床

      Volume: 60 Pages: 1408-1412

    • Related Report
      2018 Research-status Report
  • [Presentation] 【研究演題】Gene expression profiles in human keloid's differences between in vivo and in vitro (ケロイドの遺伝子発現プロファイル、in vivoとin vitroの違い)2019

    • Author(s)
      浅井幸、小池雄太、鍬塚大、宇谷厚志、室田浩之
    • Organizer
      日本皮膚科学会第338回長崎地方会例会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Microarray analysis of molecules related to keloid itch2019

    • Author(s)
      Misachi Asai, Yuta Koike, Kazuya Kashiyama, Yosuke Yagi, Yutaka Kuwatsuka,,Atsushi Utani, Hiroyuki Murota
    • Organizer
      The 10th World Congress on ITCH
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 【研究演題】PXE診療ガイドラインの公表2018

    • Author(s)
      岩永 聰、小池雄太、郡家(大久保)佑美、鍬塚 大、宇谷厚志
    • Organizer
      日本皮膚科学会第334回長崎地方会例会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] トラベクテジンの血管外漏出の1例2018

    • Author(s)
      村山直也、吉見公佑、鍬塚大、富田雅人
    • Organizer
      第117回日本皮膚科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 限界線治療歴のある被爆者に臀部有棘細胞癌が多発した1例2018

    • Author(s)
      本多舞、鍬塚さやか、鍬塚大、松田勝也、中島正洋、宇谷厚志
    • Organizer
      第117回日本皮膚科学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 当科における免疫チェックポイント阻害薬の使用経験2018

    • Author(s)
      鍬塚大
    • Organizer
      肥前皮膚カンファランス
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] HPV16陽性の肛囲Bowen病の1例2018

    • Author(s)
      藤樹祐未、本多 舞、吉見公佑、神尾芳幸、鍬塚 大、室田浩之、芦塚賢美
    • Organizer
      日本皮膚科学会第335回長崎地方会例会
    • Related Report
      2018 Research-status Report
  • [Presentation] 鼻尖部の基底細胞がんにおける深部の切除範囲について2018

    • Author(s)
      鍬塚大、岩永聰、吉見公佑、大石正雄、田中克己、室田浩之
    • Organizer
      第33回日本皮膚外科学会総会・学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 皮膚科の副作用の見方 -症状の画像スライド・皮内反応テストの実技-2018

    • Author(s)
      鍬塚大
    • Organizer
      第6回長崎薬剤師フィジカルアセスメント研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] ピロリ菌除菌中に生じたびまん性紫斑より診断に至った後天性血栓性血小板減少性紫斑病の1例2018

    • Author(s)
      福地麗雅、冨野千愛、本多 舞、鍬塚 大、室田浩之、塚崎直子
    • Organizer
      日本皮膚科学会長崎地方会第336回例会
    • Related Report
      2018 Research-status Report
  • [Presentation] 長崎県内におけるメラノーマ治療の現状-免疫チェックポイント阻害薬を中心に-2018

    • Author(s)
      鍬塚大
    • Organizer
      長崎県皮膚腫瘍カンファランス
    • Related Report
      2018 Research-status Report
  • [Presentation] Bowen病の多段階的上皮間葉転換プロセス2018

    • Author(s)
      小池雄太、與崎マリ子、鍬塚大、宇谷厚志、室田浩之
    • Organizer
      第70回日本皮膚科学会西部支部学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Endocrine mucin producing sweat gland carcinomaの1例2018

    • Author(s)
      冨野千愛、村山直也、鍬塚大、室田浩之、藤原洸平、今村禎伸、黒田揮志夫、福岡順也
    • Organizer
      第70回日本皮膚科学会西部支部学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] メルケル細胞癌との鑑別を要した多発性骨髄腫の1例2018

    • Author(s)
      岩永聰、鍬塚大、清原龍士、松下泰三、室田浩之
    • Organizer
      第70回日本皮膚科学会西部支部学術大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 悪性黒色腫の治療戦略 変革の時代へ 展望と課題2018

    • Author(s)
      鍬塚大
    • Organizer
      第9回癌・炎症と抗酸化研究会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 2018年長崎大皮膚科入院患者のまとめ2018

    • Author(s)
      小池雄太、鍬塚 大、原 肇秀、室田浩之
    • Organizer
      日本皮膚科学会第337回長崎地方会例会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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