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Elucidation of pathogenesis of Hunner type interstitial cystitis based on genomic exploration for immunological inflammation and epithelial denudation

Research Project

Project/Area Number 17H06639
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Urology
Research InstitutionThe University of Tokyo

Principal Investigator

Akiyama Yoshiyuki  東京大学, 医学部附属病院, 助教 (20529135)

Project Period (FY) 2017-08-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords網羅的遺伝子発現解析 / 慢性疼痛 / 免疫性炎症 / トランスクリプトーム解析 / バイオマーカー / ハンナ型間質性膀胱炎 / 泌尿器科学 / 間質性膀胱炎
Outline of Final Research Achievements

We performed whole-transcriptome sequencing of interstitial cystitis and bladder pain syndrome (IC/BPS). Hierarchical clustering analysis identified a distinct gene expression profile in samples from patients with IC/BPS with Hunner lesions, and subsequent pathway analysis revealed up-regulation of biological processes involving immune responses and infection in these cases. Overexpression of VEGF and BAFF in IC/BPS with Hunner lesions was confirmed by quantitative PCR and immunohistochemistry. VEGF and BAFF could serve as potential disease biomarkers or therapeutic targets for IC/BPS with Hunner lesions.

Academic Significance and Societal Importance of the Research Achievements

IC/BPSの疾患概念確立及び病態解明に向けた分子生物学的エビデンスの創出を行い、IC/BPSは大きく2群に区別される症状症候群であることを明らかにした。また、一部の病型では、病態の背景に特定の免疫学的機序またはB細胞増殖性疾患の存在が示唆されること、VEGFとBAFF蛋白の発現が特異的に上昇していることを同定した。これらの成果はIC/BPSの疾患概念・病型分類を確立させるととも、新規治療戦略の開発にも大きく寄与する可能性が高く学術的意義が高い。また、原因不明の難病に対して新規治療法の開発がなされればその社会的意義も極めて高いものとなる。本研究成果はこれらに繋がる可能性を持つものである。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • Research Products

    (20 results)

All 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 6 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 7 results,  Invited: 4 results) Book (5 results)

  • [Journal Article] Molecular Taxonomy of Interstitial Cystitis/Bladder Pain Syndrome Based on Whole Transcriptome Profiling by Next-Generation RNA Sequencing of Bladder Mucosal Biopsies2019

    • Author(s)
      Akiyama Yoshiyuki、Maeda Daichi、Katoh Hiroto、Morikawa Teppei、Niimi Aya、Nomiya Akira、Sato Yusuke、Kawai Taketo、Goto Akiteru、Fujimura Tetsuya、Fukuhara Hiroshi、Nakagawa Tohru、Igawa Yasuhiko、Ishikawa Shumpei、Fukayama Masashi、Kume Haruki、Homma Yukio
    • Journal Title

      Journal of Urology

      Volume: 印刷中 Issue: 2 Pages: 290-300

    • DOI

      10.1097/ju.0000000000000234

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pathology and terminology of interstitial cystitis/bladder pain syndrome: A review2019

    • Author(s)
      Akiyama Yoshiyuki, Homma Yukio and Maeda Daichi
    • Journal Title

      Histology and Histopathology

      Volume: 34 Pages: 25-32

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extent of Hunner lesions: The relationships with symptom severity and clinical parameters in Hunner type interstitial cystitis patients2018

    • Author(s)
      Akiyama Yoshiyuki、Niimi Aya、Nomiya Akira、Yamada Yukio、Nakagawa Tohru、Fujimura Tetsuya、Fukuhara Hiroshi、Kume Haruki、Igawa Yasuhiko、Homma Yukio
    • Journal Title

      Neurourology and Urodynamics

      Volume: 37 Issue: 4 Pages: 1441

    • DOI

      10.1002/nau.23467

    • URL

      https://pure.teikyo.jp/en/publications/7662b3a1-f0d2-4623-994b-1b05e28030bf

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Digital quantitative analysis of mast cell infiltration in interstitial cystitis.2018

    • Author(s)
      Akiyama Y, Maeda D, Morikawa T, Niimi A, Nomiya A, Yamada Y, Igawa Y, Goto A, Fukayama M, Homma Y.
    • Journal Title

      Neurourol Urodyn.

      Volume: 37 Issue: 2 Pages: 650-657

    • DOI

      10.1002/nau.23365

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Diagnostic value of urinary CXCL10 as a biomarker for predicting Hunner type interstitial cystitis2017

    • Author(s)
      Niimi Aya、Igawa Yasuhiko、Aizawa Naoki、Honma Toshiki、Nomiya Akira、Akiyama Yoshiyuki、Kamei Jun、Fujimura Tetsuya、Fukuhara Hiroshi、Homma Yukio
    • Journal Title

      Neurourol Urodyn

      Volume: 37(3) Issue: 3 Pages: 1113-1119

    • DOI

      10.1002/nau.23431

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Toll-like receptor 7 is overexpressed in the bladder of Hunner-type interstitial cystitis, and its activation in the mouse bladder can induce cystitis and bladder pain2017

    • Author(s)
      Ichihara Koji、Aizawa Naoki、Akiyama Yoshiyuki、Kamei Jun、Masumori Naoya、Andersson Karl-Erik、Homma Yukio、Igawa Yasuhiko
    • Journal Title

      Pain

      Volume: 158(8) Issue: 8 Pages: 1538-1545

    • DOI

      10.1097/j.pain.0000000000000947

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Phenotyping of Interstitial cystitis/bladder pain syndrome2019

    • Author(s)
      Yoshiyuki Akiyama
    • Organizer
      The 6th Annual Meeting of the Asia-Pacific Urogynecology Association
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Whole-Transcriptome analysis in Bladder Pain Syndrome/Interstitial Cystitis by Next-Generation sequencing: A Distinct Genomic Landscape by the phenotypes2018

    • Author(s)
      Yoshiyuki Akiyama
    • Organizer
      113th American Urological Association annual meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Subtyping and Phenotyping of IC/BPS2018

    • Author(s)
      Yoshiyuki Akiyama
    • Organizer
      The 4th International Consultation on Interstitial Cystitis, Japan
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Quantitative Histological analysis of interstitial cystitis: A novel approach to elucidate IC pathophysiology2018

    • Author(s)
      Yoshiyuki Akiyama
    • Organizer
      The 4th International Consultation On Interstitial Cystitis, Japan (ICICJ)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 間質性膀胱炎における拡張後粘膜出血の診断的意義―網羅的遺伝子発現/組織定量解析法による検討2018

    • Author(s)
      秋山佳之
    • Organizer
      第25回日本排尿機能学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Whole-Transcriptome profiling in Interstitial Cystitis and Relative diseases by Next-Generation Sequencing: A Paradigm Shift of The Disease Concept2018

    • Author(s)
      Yoshiyuki Akiyama
    • Organizer
      第106回日本泌尿器科学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Pathophysiology of Interstitial cystitis.2017

    • Author(s)
      Akiyama Yoshiyuki
    • Organizer
      112th American Urological Association (AUA) annual meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A randomized control trial on intravesical instillation of heparin versus a cocktail of heparin plus lidocaine for refractory interstitial cystitis.2017

    • Author(s)
      Nomiya Akira
    • Organizer
      47 th International Continence Society (ICS) Annual meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] INCREASE IN SPINAL FLUID LEVEL OF NEUROGENIC PAIN-RELATED LYSOPHOSPHATIDYLCHOLINES IN HUNNER TYPE INTERSTITIAL CYSTITIS2017

    • Author(s)
      Niimi Aya
    • Organizer
      47 th International Continence Society (ICS) Annual meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Book] 別冊BIO Clinica 泌尿器系疾患と慢性炎症:間質性膀胱炎について2018

    • Author(s)
      秋山佳之、前田大地
    • Total Pages
      4
    • Publisher
      北隆館
    • Related Report
      2018 Annual Research Report
  • [Book] 泌尿器外科 泌尿器慢性疾患の生活指導:間質性膀胱炎患者の生活指導2018

    • Author(s)
      秋山佳之
    • Total Pages
      3
    • Publisher
      医学図書出版株式会社
    • Related Report
      2018 Annual Research Report
  • [Book] 泌尿器外科 後期研修医がおさえておきたい泌尿器疾患TOP302017

    • Author(s)
      秋山佳之
    • Total Pages
      10
    • Publisher
      医学図書出版
    • Related Report
      2017 Annual Research Report
  • [Book] 排尿障害プラクティス2017

    • Author(s)
      秋山佳之
    • Total Pages
      3
    • Publisher
      メディカルレビュー社
    • Related Report
      2017 Annual Research Report
  • [Book] 泌尿器ケア2017

    • Author(s)
      秋山佳之
    • Total Pages
      8
    • Publisher
      メディカ出版
    • Related Report
      2017 Annual Research Report

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Published: 2017-08-25   Modified: 2020-03-30  

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