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Investigation of the mechanism of fibrosis in IgG4-related disease

Research Project

Project/Area Number 15K10818
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Otorhinolaryngology
Research InstitutionSapporo Medical University

Principal Investigator

Takano Kenichi  札幌医科大学, 医学部, 准教授 (70404689)

Co-Investigator(Kenkyū-buntansha) 松宮 弘  札幌医科大学, 医学部, 研究員 (80517904)
角木 拓也  札幌医科大学, 医学部, 研究員 (70706548)
金子 躍人  札幌医科大学, 医学部, 研究員 (90738874)
矢島 諒人  札幌医科大学, 医学部, 研究員 (90722455)
垣内 晃人  札幌医科大学, 医学部, 研究員 (60722436)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords唾液腺 / IgG4関連疾患 / 線維化 / 繊維芽細胞 / IL-6 / IgG4関連涙腺・唾液腺炎 / サイトカイン / 顎下腺 / 導管上皮 / タイト結合 / 細胞・組織 / 導管上皮細胞
Outline of Final Research Achievements

In GeneChip analysis, mRNAs of IL-6, IL-18, TSLP and MMP1 were highly expressed in the fibroblasts from SMG tissue of patients with IgG4-RD than in normal. The expression and secretion of IL-6 was greatly higher in IgG4-RD SMG fibroblasts than in normal. The expression and the secretion of IL-6 was upregulated by treatment with IL-1β, TNFα or TNFα/TGF-β. NF-κB inhibitor curcumin prevented the secretion and the expression of IL-6 induced by IL-1β or TNFα/TGF-β in the IgG4-RD SMG fibrobasts. Wnt1-inducible signaling protein 1 (WISP1) was also increased in the IgG4-RD SMG fibroblasts than in the normal. Curcumin also prevented WISP1 expression induced by IL-1β or TNFα/TGF-β in the normal. Treatment with IL-6 or WISP1 increased G2/M phase of the SMG fibroblasts in the normal. Expression of TSLP and IL-33 was increased in the IgG4-RD SMG fibroblasts than in the normal.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (22 results)

All 2018 2017 2016 2015 2014

All Journal Article (14 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 12 results,  Open Access: 6 results,  Acknowledgement Compliant: 4 results) Presentation (7 results) (of which Int'l Joint Research: 1 results) Book (1 results)

  • [Journal Article] Clinical utility of 18F-fluorodeoxyglucose/positron emission tomography in diagnosis of immunoglobulin G4-related sclerosing sialadenitis2017

    • Author(s)
      Takano Kenichi、Yajima Ryoto、Kamekura Ryuta、Yamamoto Motohisa、Takahashi Hiroki、Yama Naoya、Hatakenaka Masamitsu、Himi Tetsuo
    • Journal Title

      The Laryngoscope

      Volume: 128 Issue: 5 Pages: 1120-1125

    • DOI

      10.1002/lary.26945

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cutting Edge: A Critical Role of Lesional T Follicular Helper Cells in the Pathogenesis of IgG4-Related Disease2017

    • Author(s)
      Kamekura Ryuta、Takano Kenichi、Yamamoto Motohisa、Kawata Koji、Shigehara Katsunori、Jitsukawa Sumito、Nagaya Tomonori、Ito Fumie、Sato Akinori、Ogasawara Noriko、Tsubomatsu Chieko、Takahashi Hiroki、Nakase Hiroshi、Himi Tetsuo、Ichimiya Shingo
    • Journal Title

      The Journal of Immunology

      Volume: 199 Issue: 8 Pages: 2624-2629

    • DOI

      10.4049/jimmunol.1601507

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Recent advances in knowledge regarding the head and neck manifestations of IgG4-related disease2017

    • Author(s)
      Takano Kenichi、Yamamoto Motohisa、Takahashi Hiroki、Himi Tetsuo
    • Journal Title

      Auris Nasus Larynx

      Volume: 44 Issue: 1 Pages: 7-17

    • DOI

      10.1016/j.anl.2016.10.011

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] IgG4関連疾患の発症・病態形成のメカニズム2017

    • Author(s)
      高野 賢一
    • Journal Title

      アレルギーの臨床

      Volume: 36 Pages: 1236-1240

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Assessing the usefulness of salivary gland biopsy for diagnosis of type-1 autoimmune pancreatitis2016

    • Author(s)
      Takano K, Yamamoto M, Ichimiya S, Takahashi H, Himi T.
    • Journal Title

      Mod Rheumatol

      Volume: 18 Issue: 3 Pages: 1-3

    • DOI

      10.1080/14397595.2016.1209818

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] The Behavior and Role of Lipolysis-stimulated Lipoprotein Receptor, a Component of Tricellular Tight Junctions, in Head and Neck Squamous Cell Carcinomas2016

    • Author(s)
      Takano K, Kakuki T, Obata K, Nomura K, Miyata R, Kondo A, Kurose M, Kakiuchi A, Kaneko Y, Kohno T, Himi T, Kojima T
    • Journal Title

      Anticancer Res

      Volume: 36 Issue: 11 Pages: 5895-5904

    • DOI

      10.21873/anticanres.11176

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Clinicopathological analysis of salivary gland tissue from patients with IgG4-related disease.2016

    • Author(s)
      Takano K, Nomura K, Abe A, Kamekura R, Yamamoto M, Ichimiya S, Takahashi H, Himi T
    • Journal Title

      Acta Otolaryngol

      Volume: 未定 Issue: 7 Pages: 1-5

    • DOI

      10.3109/00016489.2016.1154605

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.2016

    • Author(s)
      Abe A, Takano K, Kojima T, Nomura K, Kakuki T, Kaneko Y, Yamamoto M, Takahashi H, Himi T
    • Journal Title

      J Mol Histol

      Volume: 未定 Issue: 3 Pages: 353-363

    • DOI

      10.1007/s10735-016-9667-2

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A case of progressively transformed germinal center-type IgG4-related lymphadenopathy.2016

    • Author(s)
      Seki N, Yamazaki N, Koizumi J, Takano K, Abe A, Ikeda T, Noguchi H, Himi T
    • Journal Title

      Auris Nasus Larynx

      Volume: 42 Issue: 4 Pages: 345-347

    • DOI

      10.1016/j.anl.2015.02.010

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical Evaluation of Sinonasal Lesions in Patients With Immunoglobulin G4-Related Disease.2015

    • Author(s)
      Takano K, Abe A, Yajima R, Kakuki T, Jitsukawa S, Nomura K, Himi T
    • Journal Title

      Ann Otol Rhinol Laryngol

      Volume: 124 Issue: 12 Pages: 965-971

    • DOI

      10.1177/0003489415593557

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Validation of the comprehensive diagnostic criteria for IgG4-related disease in a SMART registry2015

    • Author(s)
      Yamamoto M, Shimizu Y, Yajima H, Tabeya T, Suzuki C, Naishiro Y, Takano K, Murakami R, Honda S, Abe T, Himi T, Mukai M, Takahashi H
    • Journal Title

      Mod Rheumatol.

      Volume: 25 Issue: 2 Pages: 199-204

    • DOI

      10.3109/14397595.2015.1069951

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] IgG4関連疾患と唾液腺炎2015

    • Author(s)
      高野賢一
    • Journal Title

      ENTONI

      Volume: 177 Pages: 63-69

    • Related Report
      2015 Research-status Report
  • [Journal Article] Everyday clinical practice in IgG4-related dacryoadenitis and/or sialadenitis: Results from the SMART database.2014

    • Author(s)
      Yamamoto M, Yajima H, Takahashi H, Yokoyama Y, Ishigami K, Shimizu Y, Tabeya T, Suzuki C, Naishiro Y, Takano KI, Yamashita K, Hashimoto M, Keira Y, Honda S, Abe T, Suzuki Y, Mukai M,Himi T, Hasegawa T, Imai K, Shinomura Y
    • Journal Title

      Mod Rheumatol

      Volume: 27 Issue: 2 Pages: 1-6

    • DOI

      10.3109/14397595.2014.950036

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Identification of relapse predictors in IgG4-related disease using multivariate analysis of clinical data at the first visit and initial treatment.2014

    • Author(s)
      Yamamoto M, Yajima H, Takahashi H, Yokoyama Y, Ishigami K, Shimizu Y, Tabeya T, Suzuki C, Naishiro Y, Takano KI, Yamashita K, Hashimoto M, Keira Y, Honda S, Abe T, Suzuki Y, Mukai M,Himi T, Hasegawa T, Imai K, Shinomura Y
    • Journal Title

      Rheumatology

      Volume: 54 Issue: 1 Pages: 45-49

    • DOI

      10.1093/rheumatology/keu228

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] IgG4関連疾患における顎下腺の線維化メカニズムの解析2018

    • Author(s)
      矢島諒人,高野賢一,氷見徹夫,小島隆
    • Organizer
      第36回日本耳鼻咽喉科免疫アレルギー学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] IgG4関連唾液腺炎の診断におけるPET/CT検査の有用性2017

    • Author(s)
      高野 賢一, 矢島 諒人, 亀倉 隆太, 大國 毅, 黒瀬 誠, 伊藤 史恵, 坪松 ちえ子, 氷見 徹夫
    • Organizer
      第30回日本口腔・咽頭科学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] IgG4関連疾患におけるPET/CT検査の有用性とピットフォール2017

    • Author(s)
      高野 賢一, 矢島 諒人, 亀倉 隆太, 氷見 徹夫
    • Organizer
      第118回日本耳鼻咽喉科学会総会・学術講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] IgG4関連疾患における線維化関連因子の検討2016

    • Author(s)
      高野賢一,矢島諒人,亀倉隆太,坪松ちえ子,氷見徹夫
    • Organizer
      日本耳鼻咽喉科口腔・咽頭科学会
    • Place of Presentation
      松江テルサ(島根県松江市)
    • Year and Date
      2016-09-08
    • Related Report
      2016 Research-status Report
  • [Presentation] Recent advances in IgG4-related sialadenitis2015

    • Author(s)
      Takano K, Nomura K, Abe A, Himi T
    • Organizer
      13th Japan-Taiwan Conference on Otolaryngology Head and Neck Surgery
    • Place of Presentation
      一橋大学(東京都千代田区)
    • Year and Date
      2015-12-03
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] IgG4関連疾患における唾液腺生検に関する検討2015

    • Author(s)
      高野賢一,野村一顕,阿部亜由美,亀倉隆太
    • Organizer
      第24回日本シェーグレン症候群学会
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2015-09-18
    • Related Report
      2015 Research-status Report
  • [Presentation] IgG4関連疾患における唾液腺生検に関する検討2015

    • Author(s)
      高野賢一,野村一顕,阿部亜由美,亀倉隆太
    • Organizer
      第28回日本口腔・咽頭科学会
    • Place of Presentation
      ホテル阪神(大阪市福島区)
    • Year and Date
      2015-09-10
    • Related Report
      2015 Research-status Report
  • [Book] ENT臨床フロンティア 耳鼻咽喉科イノベーション2016

    • Author(s)
      高野賢一,氷見徹夫
    • Total Pages
      4
    • Publisher
      中山書店
    • Related Report
      2016 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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