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Identification of fibroblasts that differentiate into myofibroblasts and the control of organ fibrosis

Research Project

Project/Area Number 16K08736
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Iwashita Toshihide  浜松医科大学, 医学部, 教授 (00283432)

Co-Investigator(Kenkyū-buntansha) 目黒 史織  浜松医科大学, 医学部, 助教 (40724290)
Project Period (FY) 2016-04-01 – 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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
KeywordsFibroblast / lung / fibrosis / pulmonary fibrosis / 線維芽細胞 / Sca1 / collagen / elastin / CD248 / integrin alpha 8 / 線維化 / 臓器線維症 / Thy1 / collagen 1a1 / 線維芽細胞のheterogeneity / 筋線維芽細胞 / 炎症
Outline of Final Research Achievements

To better understand the pathology and improve diagnosis and treatment of lung fibrosis, it is necessary to elucidate the nature of lung fibroblast heterogeneity and identify markers for the classification of human lung fibroblast subtypes. We characterized distinct mouse lung fibroblast subpopulations and performed microarray analysis to identify molecular markers. Based on the expression of these markers, in normal human lungs and idiopathic pulmonary fibrosis (IPF) lungs, two corresponding major fibroblast subtypes were identified: CD248-positive fibroblast and ITGA8-positive fibroblast, localized in the collagen fiber-rich connective tissue and in the elastic fiber-rich connective tissue, respectively. This human lung fibroblast classification may be helpful for further detailed investigations of the functions of lung fibroblast subtypes, which can provide new insights into lung development and the pathological processes underlying fibrotic lung diseases.

Academic Significance and Societal Importance of the Research Achievements

今回明らかにしたヒト肺線維芽細胞の分類システム(CD248陽性線維芽細胞およびITGA8陽性線維芽細胞)を使用して、異なる線維芽細胞の機能のさらなる詳細な調査を行うことができる。それは肺発生や特発性肺線維症だけではなく、非特異的間質性肺炎やおよびpleuroparenchymal fibroelastosisなどの他の線維性肺疾患の根底にある病理学的過程に関する新たな洞察を得るのに役立つと考えられる。

Report

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

    (19 results)

All 2018 2017 2016

All Journal Article (16 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 16 results,  Open Access: 11 results,  Acknowledgement Compliant: 6 results) Presentation (3 results)

  • [Journal Article] Podoplanin-positive myofibroblasts: a pathological hallmark of pleuroparenchymal fibroelastosis.2018

    • Author(s)
      Enomoto Y, Matsushima S, Meguro S, Kawasaki H, Kosugi I, Fujisawa T, Enomoto N, Inui N, Nakamura Y, Suda T, Iwashita T.
    • Journal Title

      Histopathology.

      Volume: 印刷中 Issue: 7 Pages: 1209-1215

    • DOI

      10.1111/his.13494

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] LTBP2 is secreted from lung myofibroblasts and is a potential biomarker for idiopathic pulmonary fibrosis2018

    • Author(s)
      Enomoto Yasunori、Matsushima Sayomi、Shibata Kiyoshi、Aoshima Yoichiro、Yagi Haruna、Meguro Shiori、Kawasaki Hideya、Kosugi Isao、Fujisawa Tomoyuki、Enomoto Noriyuki、Inui Naoki、Nakamura Yutaro、Suda Takafumi、Iwashita Toshihide
    • Journal Title

      Clinical Science

      Volume: 132 Issue: 14 Pages: 1565-1580

    • DOI

      10.1042/cs20180435

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] MHC class I in dopaminergic neurons suppresses relapse to reward seeking2018

    • Author(s)
      Murakami G, Edamura M, Furukawa T, Kawasaki H, Kosugi I, Fukuda A, Iwashita T, Nakahara D
    • Journal Title

      Science Advances

      Volume: 4 Issue: 3 Pages: 7388-7388

    • DOI

      10.1126/sciadv.aap7388

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunohistochemical examination using the pericyte marker myosin 1B in a perivascular myoid tumor of soft tissue with definitive pericytic differentiation.2018

    • Author(s)
      Meguro S, Matsushima S, Enomoto Y, Kawasaki H, Kosugi I, Tsuchida T, Baba S, Fukamizu H, Yamato Y, Iwashita T.
    • Journal Title

      Patholology International

      Volume: 69 Issue: 4 Pages: 246-248

    • DOI

      10.1111/pin.12777

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mesothelial/monocytic incidental cardiac excrescence with bone marrow.2018

    • Author(s)
      Yagi H, Takahashi S, Shinmura K, Iwashita T, Ogawa H.
    • Journal Title

      Pathol Int.

      Volume: 印刷中 Issue: 7 Pages: 436-438

    • DOI

      10.1111/pin.12661

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical diagnosis of idiopathic pleuroparenchymal fibroelastosis: A retrospective multicenter study.2017

    • Author(s)
      Enomoto Y, Nakamura Y, Satake Y, Sumikawa H, Johkoh T, Colby TV, Yasui H, Hozumi H, Karayama M, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Inui N, Iwashita T, Kuroishi S, Yokomura K, Koshimizu N, Toyoshima M, Imokawa S, Yamada T, Shirai T, Hayakawa H, Suda T.
    • Journal Title

      Respir Med.

      Volume: 133 Pages: 1-5

    • DOI

      10.1016/j.rmed.2017.11.003

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] A case of a primary hepatic so-called adenosarcoma with heterotopic ossification: possibly of biliary adenofibroma origin.2017

    • Author(s)
      Meguro S, Yamazaki S, Matsushima S, Kawata K, Kawasaki H, Tsuchida T, Kosugi I, Kobayashi Y, Baba S, Iwashita T.
    • Journal Title

      Hum Pathol.

      Volume: 73 Pages: 108-113

    • DOI

      10.1016/j.humpath.2017.10.009

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Evaluation of epigenetic inactivation of vascular endothelial growth factor receptors in head and neck squamous cell carcinoma.2017

    • Author(s)
      Misawa Y, Misawa K, Kawasaki H, Imai A, Mochizuki D, Ishikawa R, Endo S, Mima M, Kanazawa T, Iwashita T, Mineta H.
    • Journal Title

      Tumour Biol.

      Volume: 39 Issue: 7 Pages: 1-15

    • DOI

      10.1177/1010428317711657

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiologic pleuroparenchymal fibroelastosis-like lesion in connective tissue disease-related interstitial lung disease.2017

    • Author(s)
      Enomoto Y, Nakamura Y, Colby TV, Johkoh T, Sumikawa H, Nishimoto K, Yoshimura K, Matsushima S, Oyama Y, Hozumi H, Kono M, Fujisawa T, Enomoto N, Inui N, Iwashita T, Suda T.
    • Journal Title

      PLoS One

      Volume: 12 Issue: 6 Pages: e0180283-e0180283

    • DOI

      10.1371/journal.pone.0180283

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Digoxin Attenuates Murine Experimental Colitis by Downregulating Th17-related Cytokines.2017

    • Author(s)
      Tani S, Takano R, Tamura S, Oishi S, Iwaizumi M, Hamaya Y, Takagaki K, Nagata T, Seto S, Horii T, Kosugi I, Iwashita T, Osawa S, Furuta T, Miyajima H, Sugimoto K.
    • Journal Title

      Inflamm Bowel Dis.

      Volume: 23 Issue: 5 Pages: 728-738

    • DOI

      10.1097/mib.0000000000001096

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Phenotypic characterization of perivascular myoid cell neoplasms, using myosin 1B, a newly identified human pericyte marker2017

    • Author(s)
      Shiori Meguro, Taisuke Akamatsu, Sayomi Matsushima, Isao Kosugi, Hideya Kawasaki, Yoshifumi Arai, Satoshi Baba, Takashi Tsuchida, Yoji Shido, Takafumi Suda, Toshihide Iwashita
    • Journal Title

      Human Pathology

      Volume: 62 Pages: 187-198

    • DOI

      10.1016/j.humpath.2016.12.024

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Clinical significance of soluble CD163 in polymyositis-related or dermatomyositis-related interstitial lung disease2017

    • Author(s)
      Enomoto Y, Suzuki Y, Hozumi H, Mori K, Kono M, Karayama M, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Suzuki D, Ogawa N, Nakashima R, Mimori T, Iwashita T, Suda T
    • Journal Title

      Arthritis Res Ther

      Volume: 19 Issue: 1 Pages: 9-9

    • DOI

      10.1186/s13075-016-1214-8

    • NAID

      120005973333

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Phenotypic characterization of perivascular myoid cell neoplasms, using myosin 1B, a newly identified human pericyte marker.2017

    • Author(s)
      Meguro S, Akamatsu T, Matsushima S, Kosugi I, Kawasaki H, Arai Y, Baba S, Tsuchida T, Shido Y, Suda T, Iwashita T.
    • Journal Title

      Human Pathology

      Volume: 62 Pages: 187-198

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Pathogenesis of developmental anomalies of the central nervous system induced by congenital cytomegalovirus infection.2017

    • Author(s)
      Kawasaki H, Kosugi I, Meguro S, Iwashita T.
    • Journal Title

      Pathol Int,

      Volume: 67 Pages: 72-82

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Pathogenesis of developmental anomalies of the central nervous system induced by congenital cytomegalovirus infection.2016

    • Author(s)
      Kawasaki H, Kosugi I, Meguro S, Iwashita T.
    • Journal Title

      Pathol Int.

      Volume: 67(2) Issue: 2 Pages: 72-82

    • DOI

      10.1111/pin.12502

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Intracerebroventricular and Intravascular Injection of Viral Particles and Fluorescent Microbeads into the Neonatal Brain.2016

    • Author(s)
      Kawasaki H, Kosugi I, Sakao-Suzuki M, Meguro S, Tsutsui Y, Iwashita T.
    • Journal Title

      J Vis Exp.

      Volume: 24;(113) Issue: 113 Pages: 113-113

    • DOI

      10.3791/54164

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] NanoSuit法を利用した高精度な迅速ウイルス粒子定量・同定法の開発、2017

    • Author(s)
      河崎秀陽、髙久康春、太田勲、小杉伊三夫、目黒史織、筒井祥博、針山孝彦、岩下寿秀、
    • Organizer
      第106回日本病理学会
    • Related Report
      2017 Research-status Report
  • [Presentation] NanoSuit法を利用した高精度な迅速ウイルス定量・同定法の開発、2017

    • Author(s)
      河崎秀陽、髙久康春、太田勲、小杉伊三夫、目黒史織、岩下寿秀、針山孝彦、
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] マウス肺における異なった種類の線維芽細胞の同定2016

    • Author(s)
      松島 紗代実、目黒 史織、河崎 秀陽、小杉 伊三夫、岩下 寿秀
    • Organizer
      105回日本病理学会総会
    • Place of Presentation
      仙台
    • Year and Date
      2016-05-12
    • Related Report
      2016 Research-status Report

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

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