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Investigation of pathophysiologies by genomic analyses in interstitial cystitis

Research Project

Project/Area Number 16H05463
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionThe University of Tokyo

Principal Investigator

Homma Yukio  東京大学, 医学部附属病院, 登録診療員 (40165626)

Co-Investigator(Kenkyū-buntansha) 新美 文彩  東京大学, 医学部附属病院, 登録診療員 (00376451)
前田 大地  大阪大学, 医学系研究科, 特任教授(常勤) (30585500)
井川 靖彦  東京大学, 医学部附属病院, 特任教授 (40159588)
石川 俊平  東京医科歯科大学, 難治疾患研究所, 教授 (50418638)
伊藤 雅史  地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (80393114)
森川 鉄平  東京大学, 大学院医学系研究科(医学部), 客員研究員 (80451772)
相澤 直樹  東京大学, 医学部附属病院, 特任講師 (80595257)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2017: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥10,270,000 (Direct Cost: ¥7,900,000、Indirect Cost: ¥2,370,000)
Keywords間質性膀胱炎 / 膀胱痛症候群 / RNA-seq / レパートリー解析 / マイクロRNA / ゲノミクス解析 / 免疫レパトワ解析 / ハンナ型間質性膀胱炎 / 泌尿器科学 / 排尿機能学 / 肥満細胞 / miRNA
Outline of Final Research Achievements

We performed immune repertoire analyses and whole-transcriptome sequencing for interstitial cystitis and bladder pain syndrome (IC/BPS). Clonal expansion of infiltrating T and B lymphocytes was confirmed. Especially, B cell clonal expansion was characteristic feature of 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

原因不明の指定難病であるハンナ型間質性膀胱炎において、その病態に特定の免疫応答が関与している可能性を突き止めるとともに、病態特異的な変動遺伝子及び生物学的経路としてVEGF,BAFFシグナル伝達系遺伝子群/経路を同定した本研究成果は病態解明はもとより、治療標的やバイオマーカーの創出につながる可能性があり、難治性疾患の治療・診断の向上に寄与する可能性が高い。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • Research Products

    (35 results)

All 2019 2018 2017 2016 2015

All Journal Article (14 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 14 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (18 results) (of which Int'l Joint Research: 12 results,  Invited: 7 results) Book (3 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] Pathophysiology of the underactive bladder.2017

    • Author(s)
      Aizawa N, Igawa Y
    • Journal Title

      Investig Clin Urol

      Volume: 58(Suppl 2) Issue: Suppl 2 Pages: S82-S82

    • DOI

      10.4111/icu.2017.58.s2.s82

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effect of cerebrospinal fluid shunt surgery on lower urinary tract dysfunction in idiopathic normal pressure hydrocephalus2017

    • Author(s)
      Aruga Seiji、Kuwana Nobumasa、Shiroki Yoshiharu、Takahashi Shintaro、Samejima Naoyuki、Watanabe Akira、Seki Yojiro、Igawa Yasuhiko、Homma Yukio
    • Journal Title

      Neurourol Urodyn

      Volume: 37(3) Issue: 3 Pages: 1053-1059

    • DOI

      10.1002/nau.23399

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Direct influence of systemic desensitization by resiniferatoxin on the activities of Aδ- and C-fibers in the rat primary bladder mechanosensitive afferent nerves.2016

    • Author(s)
      Aizawa N, Fukuhara H, Fujimura T, Homma Y, Igawa Y.
    • Journal Title

      Int J Urol

      Volume: 23 Issue: 11 Pages: 952-956

    • DOI

      10.1111/iju.13181

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] URB937, a peripherally restricted inhibitor for fatty acid amide hydrolase, reduces prostaglandin E2 -induced bladder overactivity and hyperactivity of bladder mechano-afferent nerve fibres in rats.2016

    • Author(s)
      Aizawa N, Gandaglia G, Hedlund P, Fujimura T, Fukuhara H, Montorsi F, Homma Y, Igawa Y.
    • Journal Title

      BJU International

      Volume: 117 Pages: 821-8

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Functional roles of bladder alpha1-adrenoceptors in the activation of single-unit primary bladder afferent activity in rats.2016

    • Author(s)
      Aizawa N, Sugiyama R, Ichihara K, Fujimura T, Fukuhara H, Homma Y, Igawa Y.
    • Journal Title

      BJU International

      Volume: 117 Issue: 2 Pages: 993-1001

    • DOI

      10.1016/j.eururo.2010.10.035

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased CXCR3 expression of infiltrating plasma cells in Hunner type interstitial cystitis.2016

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

      Scientific Report

      Volume: 6 Issue: 1 Pages: 28652-28652

    • DOI

      10.1038/srep28652

    • NAID

      120007089053

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical guidelines for interstitial cystitis and hypersensitive bladder updated in 20152016

    • Author(s)
      Homma Y, Ueda T, Tomoe H, Lin AT, Kuo HC, Lee MH, Oh SJ, Kim JC, Lee KS.
    • Journal Title

      Int J Urol

      Volume: 23 Issue: 7 Pages: 542-549

    • DOI

      10.1111/iju.13118

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hydrodistension with or without fulguration of hunner lesions for interstitial cystitis: Long-term outcomes and prognostic predictors.2015

    • Author(s)
      Niimi A, Nomiya A, Yamada Y, Suzuki M, Fujimura T, Fukuhara H, Kume H, Igawa Y, Homma Y.
    • Journal Title

      Neurourology and Urodynamics

      Volume: e-pub Issue: 8 Pages: 965-9

    • DOI

      10.1002/nau.22837

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Inhibitory effects of retigabine, a Kv7 channel activator, on mechanosensitive primary bladder afferent activities and nociceptive behaviors in rats.2015

    • Author(s)
      Aizawa N, Wakamatsu D, Kida J, Otsuki T, Saito Y, Matsuya H, Homma Y, Igawa Y.
    • Journal Title

      Neurourol Urodyn.

      Volume: in press Issue: 2 Pages: 280-285

    • DOI

      10.1002/nau.22920

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [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] 間質栄膀胱炎の膀胱内注入療法と神経変調療法2019

    • Author(s)
      新美 文彩
    • Organizer
      第107回日本泌尿器科学会総会
    • Related Report
      2018 Annual Research Report
    • 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
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [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] Take Home Message (Plenary Session)2018

    • Author(s)
      新美 文彩
    • Organizer
      第25回日本排尿機能学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ハンナ型間質性膀胱炎に対する神経障害性疼痛関連物質であるリゾリ ン脂質の関与2018

    • Author(s)
      新美 文彩
    • Organizer
      第106回日本泌尿器科学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Afferent neuromodulators of the lower urinary tract as new pharmacological targets: TRP channels.2018

    • Author(s)
      Igawa Yasuhiko
    • Organizer
      6th International Neuro-Urology Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effects of tadalafil, a PDE type 5 inhibitor, on the bladder mechanosensitive afferent activities related to microcontractions in male rats with bladder outlet obstruction.2017

    • Author(s)
      Aizawa Naoki
    • Organizer
      47 th International Continence Society (ICS) Annual meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] KPR-2579, a novel TRPM8 antagonist, inhibits acetic-acid-induced bladder hyperactivity via mechanosensitive afferent C-fibers in rats.2017

    • Author(s)
      Aizawa Naoki
    • Organizer
      47 th International Continence Society (ICS) Annual meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [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] 1.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
  • [Presentation] INFLAMMATORY INFILTRATES SPECIFIC TO HUNNER TYPE INTERSTITIAL CYSTITIS.2016

    • Author(s)
      Akiyama Y, Morikawa T, Maeda D, Niimi A, Nomiya A, Igawa Y, Fukayama M, Homma Y
    • Organizer
      46th International Continence Society (ICS) annual meeting
    • Place of Presentation
      東京、日本
    • Year and Date
      2016-09-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] INCREASED CXCR3 EXPRESSION OF INFILTRATING PLASMA CELLS IN HUNNER TYPE INTERSTITIAL CYSTITIS2016

    • Author(s)
      Akiyama Y, Maeda D, Morikawa T, Goto A, Igawa Y, Fukayama M, Homma Y
    • Organizer
      46th International Continence Society (ICS) annual meeting.
    • Place of Presentation
      東京、日本
    • Year and Date
      2016-09-13
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Frequent expansion of clonal B-cells suggestive of specific immune responses in Hunner type interstitial cystitis.2016

    • Author(s)
      Akiyama Y, Maeda D, Morikawa T, Niimi A, Nomiya A, Yamada Y, Kamei J, Aizawa N, Igawa Y, Fukayama M, Homma Y
    • Organizer
      111th American Urological Association annual meeting.
    • Place of Presentation
      San diego, USA.
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] シンポジウム「はじめてのFemale Urology」間質性膀胱炎2016

    • Author(s)
      新美 文彩
    • Organizer
      第81回 日本泌尿器科学会東部総会
    • Place of Presentation
      秋田、日本
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 教育セミナー(日本排尿機能学会認定医申請教育講演)「Female LUTS update-間質性膀胱炎2016

    • Author(s)
      新美 文彩
    • Organizer
      第23回 日本排尿機能学会
    • Place of Presentation
      東京、日本
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Book] 別冊BIO Clinica2018

    • 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
    • Related Report
      2018 Annual Research Report
  • [Book] 泌尿器Care and Cure Urolo2018

    • Author(s)
      新美文彩
    • Total Pages
      4
    • Publisher
      メディカ出版
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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