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Organ-specificity of lung fibroblast and its relationship to lung disease

Research Project

Project/Area Number 18K08170
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53030:Respiratory medicine-related
Research InstitutionThe University of Tokyo

Principal Investigator

Saito Akira  東京大学, 医学部附属病院, 講師 (90591412)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords線維芽細胞 / 肺線維症 / 肺癌 / 転写因子 / スーパーエンハンサー / TBX4 / FOXL1 / 肺線維芽細胞 / RNAシーケンス / 遺伝子発現解析 / トランスクリプトーム / 転写制御 / 呼吸器疾患
Outline of Final Research Achievements

By comparing the gene expression profiles derived from different organs, we identified eight transcription factors that show relatively higher expression and are associated with super-enhancers (TBX2, TBX4, TBX5, HOXA5, FOXL1, FOXP1, MEIS1 and TGIF1). TBX4 functions as a master transcription factor in lung fibroblasts. TBX4 expression is downregulated by TGF-beta and is lower in lung cancer-associated fibroblasts. Highly activated FOX gene cluster (FOXL1, FOXC2 and FOXF1) is a hallmark of lung fibroblasts. FOXL1 is involved in the regulation of TAZ/YAP and BMP signaling, and its expression is higher in pulmonary fibrosis. Transcription factors unique to lung fibroblasts are involved in the pathogenesis of lung cancer or pulmonary fibrosis.

Academic Significance and Societal Importance of the Research Achievements

肺組織に由来する線維芽細胞において、組織特異的に発現している遺伝子群を同定し、機能的に重要性が高いと思われる転写因子(TBX4およびFOXL1)を選定し、その生理的・病理的な役割を検討した。これらの転写因子は肺癌や肺線維症において発現変化がみられており、これらの疾患の分子病態に関与している可能性がある。

Report

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

    (19 results)

All 2020 2019 2018 Other

All Int'l Joint Research (7 results) Journal Article (12 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 12 results,  Open Access: 6 results)

  • [Int'l Joint Research] Massachusetts Institute of Technology(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of North Carolina(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Uppsala University(スウェーデン)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Lund University(スウェーデン)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] McGill University Health Center(カナダ)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Massachusetts Institute of Technology(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] University of North Carolina(米国)

    • Related Report
      2019 Research-status Report
  • [Journal Article] FOXL1 Regulates Lung Fibroblast Function via Multiple Mechanisms2020

    • Author(s)
      Miyashita Naoya、Horie Masafumi、Suzuki Hiroshi I.、Saito Minako、Mikami Yu、Okuda Kenichi、Boucher Richard C.、Suzukawa Maho、Hebisawa Akira、Saito Akira、Nagase Takahide
    • Journal Title

      American Journal of Respiratory Cell and Molecular Biology

      Volume: 63 Issue: 6 Pages: 831-842

    • DOI

      10.1165/rcmb.2019-0396oc

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A mouse model of asthma‐chronic obstructive pulmonary disease overlap induced by intratracheal papain2020

    • Author(s)
      Fukuda Kensuke、Matsuzaki Hirotaka、Mikami Yu、Makita Kosuke、Miyakawa Kazuko、Miyashita Naoya、Hosoki Keisuke、Ishii Takashi、Noguchi Satoshi、Urushiyama Hirokazu、Horie Masafumi、Mitani Akihisa、Yamauchi Yasuhiro、Shimura Eri、Nakae Susumu、Saito Akira、Nagase Takahide、Hiraishi Yoshihisa
    • Journal Title

      Allergy

      Volume: 76 Issue: 1 Pages: 390-394

    • DOI

      10.1111/all.14528

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ASCL1 promotes tumor progression through cell-autonomous signaling and immune modulation in a subset of lung adenocarcinoma2020

    • Author(s)
      Miyashita N, Horie M, Mikami Y, Urushiyama H, Fukuda K, Miyakawa K, Matsuzaki H, Makita K, Morishita Y, Harada H, Backman M, Lindskog C, Brunnstr;m H, Micke P, Nagase T, Saito A.
    • Journal Title

      Cancer Lett

      Volume: 489 Pages: 121-132

    • DOI

      10.1016/j.canlet.2020.06.002

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Exophilin-5 regulates allergic airway inflammation by controlling IL-33-mediated Th2 responses2020

    • Author(s)
      Katsuhide Okunishi, Hao Wang, Maho Suzukawa, Ray Ishizaki, Eri Kobayashi, Miho Kihara, Takaya Abe, Jun-ichi Miyazaki, Masafumi Horie, Akira Saito, Hirohisa Saito, Susumu Nakae, Tetsuro Izumi
    • Journal Title

      Journal of Clinical Investigation

      Volume: - Issue: 7 Pages: 3919-3935

    • DOI

      10.1172/jci127839

    • NAID

      40022605127

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pleural thickening on screening chest X-rays: a single institutional study.2019

    • Author(s)
      Saito A, Hakamata Y, Yamada Y, Sunohara M, Tarui M, Murano Y, Mitani A, Tanaka K, Nagase T, Yanagimoto S.
    • Journal Title

      Respir Res

      Volume: 20(1) Issue: 1 Pages: 138-138

    • DOI

      10.1186/s12931-019-1116-9

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An integrative transcriptome analysis reveals a functional role for thyroid transcription factor-1 in small cell lung cancer.2018

    • Author(s)
      Horie M, Miyashita N, Mattsson JSM, Mikami Y, Sandelin M, Brunnstrom H, Micke P, Nagase T, Saito A.
    • Journal Title

      J Pathol

      Volume: 246(2) Issue: 2 Pages: 154-165

    • DOI

      10.1002/path.5109

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] An Integrative Analysis of Transcriptome and Epigenome Features of ASCL1-Positive Lung Adenocarcinomas.2018

    • Author(s)
      Miyashita N, Horie M, Suzuki HI, Yoshihara M, Djureinovic D, Persson J, Brunnstrom H, Lindskog C, Elfving H, Micke P, Saito A, Nagase T.
    • Journal Title

      J Thorac Oncol

      Volume: 13(11) Issue: 11 Pages: 1676-1691

    • DOI

      10.1016/j.jtho.2018.07.096

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling.2018

    • Author(s)
      Suzuki HI, Horie M, Mihira H, Saito A.
    • Journal Title

      J Vis Exp

      Volume: Aug 3 Issue: 138 Pages: 138-138

    • DOI

      10.3791/57577

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Classification of lung adenocarcinoma transcriptome subtypes from pathological images using deep convolutional networks2018

    • Author(s)
      3.Antonio, V. A. A., Ono, N., Saito, A., Sato, T., Altaf-Ul-Amin, M., & Kanaya, S.
    • Journal Title

      International journal of computer assisted radiology and surgery

      Volume: 13(12) Issue: 12 Pages: 1905-1913

    • DOI

      10.1007/s11548-018-1835-2

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TGF-β Signaling in Lung Health and Disease.2018

    • Author(s)
      Saito A, Horie M, Nagase T.
    • Journal Title

      Int J Mol Sci

      Volume: 19(8) Issue: 8 Pages: 2460-2460

    • DOI

      10.3390/ijms19082460

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Role of TGF-β Signaling in Lung Cancer Associated with Idiopathic Pulmonary Fibrosis.2018

    • Author(s)
      Saito A, Horie M, Micke P, Nagase T.
    • Journal Title

      Int J Mol Sci

      Volume: 19(11) Issue: 11 Pages: 3611-3611

    • DOI

      10.3390/ijms19113611

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] YAP/TAZ Signaling as a Molecular Link between Fibrosis and Cancer.2018

    • Author(s)
      Noguchi S, Saito A, Nagase T.
    • Journal Title

      Int J Mol Sci

      Volume: 19(11) Issue: 11 Pages: 3674-3674

    • DOI

      10.3390/ijms19113674

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access

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

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