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Dynamics of epithelial stem cells upon wounding

Research Project

Project/Area Number 17K16317
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Dermatology
Research InstitutionHokkaido University

Principal Investigator

Natsuga Ken  北海道大学, 大学病院, 講師 (70645457)

Research Collaborator Watanabe Mika  
Fujimura Yu  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords創傷治癒 / 表皮 / 毛包 / 幹細胞 / 再生医学
Outline of Final Research Achievements

In wounds in which the epidermis was selectively removed, there was 1 -3 reepithelialization at 24 hours after wounding as visible through HE staining. The basal layer of the epidermis expressing α6 integrin was present at this point, and cells in the re-epithelialized layer were stained with pan-cytokeratin. Loricrin staining, showing differentiation into epidermal granular layer, was not seen 48 hours after wound creation but was confirmed 72 hours later. HE staining also shows no granular layer at 48 hours after wounding, but at 72 hours after wounding, the final reepithelialization is complete. Lineage tracing also revealed that daughter cells of hair follicle upper stem cells are involved in wound reepithelialization.

Academic Significance and Societal Importance of the Research Achievements

創傷は、病原体の繁殖に伴い感染母地となるとともに、皮膚癌の発生基点ともなりうることから、人類の健康維持において制御すべき非常に重要な疾患である。本研究で確立した実験系は、実験動物を使いつつ、再現性のある表皮選択的除去が可能であり、新しい創傷実験である。この方法をlinage tracingや薬物投与実験と組み合わせることで、上皮創傷の治癒促進因子を探索することが可能となる。特に、転倒の頻度が高い高齢者の皮膚創傷や、自己免疫性・遺伝性水疱性疾患などの患者に対する治療法開発へとつなげることができる。

Report

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

    (34 results)

All 2019 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (25 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 25 results,  Open Access: 6 results) Presentation (5 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Int'l Joint Research] トリノ大学(イタリア)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] キングズカレッジロンドン(英国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] トリノ大学(イタリア)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2017 Research-status Report
  • [Journal Article] Mutant Lef1 controls Gata6 in sebaceous gland development and cancer2019

    • Author(s)
      Oules Benedicte、Rognoni Emanuel、Hoste Esther、Goss Georgina、Fiehler Ryan、Natsuga Ken、Quist Sven、Mentink Remco、Donati Giacomo、Watt Fiona M
    • Journal Title

      The EMBO Journal

      Volume: 印刷中 Issue: 9

    • DOI

      10.15252/embj.2018100526

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Fc-binding proteins enhance autoantibody-induced BP180 depletion in pemphigoid2019

    • Author(s)
      Iwata H, Kamaguchi M, Ujiie H, Ujiie I, Natsuga K, Nishie W, ShimizuH:
    • Journal Title

      J Pathol

      Volume: 247 Issue: 3 Pages: 371-380

    • DOI

      10.1002/path.5196

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bullous Pemphigoid IgG Induces Cell Dysfunction and Enhances the Motility of Epidermal Keratinocytes via Rac1/Proteasome Activation2019

    • Author(s)
      Tie Duerna、Da Xia、Natsuga Ken、Yamada Nanako、Yamamoto Osamu、Morita Eishin
    • Journal Title

      Frontiers in Immunology

      Volume: 10 Pages: 200-200

    • DOI

      10.3389/fimmu.2019.00200

    • NAID

      120007002182

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The direct binding of collagen XVII and collagen IV is disrupted by pemphigoid autoantibodies2018

    • Author(s)
      Kamaguchi Mayumi、Iwata Hiroaki、Nishie Wataru、Toyonaga Ellen、Ujiie Hideyuki、Natsuga Ken、Kitagawa Yoshimasa、Shimizu Hiroshi
    • Journal Title

      Laboratory Investigation

      Volume: 99 Issue: 1 Pages: 48-57

    • DOI

      10.1038/s41374-018-0113-9

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulatory T-cell dysfunction induces autoantibodies to bullous pemphigoid antigens in mice and human subjects2018

    • Author(s)
      Muramatsu Ken、Ujiie Hideyuki、Kobayashi Ichiro、Nishie Wataru、Izumi Kentaro、Ito Takamasa、Yoshimoto Norihiro、Natsuga Ken、Iwata Hiroaki、Shimizu Hiroshi
    • Journal Title

      Journal of Allergy and Clinical Immunology

      Volume: 142 Issue: 6 Pages: 1818-1830.e6

    • DOI

      10.1016/j.jaci.2018.03.014

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel COL7A1 mutation in a family with bullous dermolysis of the newborn: Phenotypic variability associated with a COL7A1 mutation within the same family2018

    • Author(s)
      Takashima Shota、Shinkuma Satoru、Fujita Yasuyuki、Natsuga Ken、Nomura Toshifumi、Hida Tokimasa、Ishikawa Shuku、Nakamura Hideki、Abe Riichiro、Shimizu Hiroshi
    • Journal Title

      The Journal of Dermatology

      Volume: 印刷中 Issue: 9

    • DOI

      10.1111/1346-8138.14287

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] High Expression of Collagen XVII Compensates for Its Depletion Induced by Pemphigoid IgG in the Oral Mucosa.2018

    • Author(s)
      Kamaguchi M, Iwata H, Ujiie H, Natsuga K, Nishie W, Kitagawa Y, Shimizu H.
    • Journal Title

      J Invest Dermatol.

      Volume: - Issue: 8 Pages: 1707-1715

    • DOI

      10.1016/j.jid.2018.03.002

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Intravenous IgG Reduces Pathogenic Autoantibodies, Serum IL-6 Levels, and Disease Severity in Experimental Bullous Pemphigoid Models2018

    • Author(s)
      Sasaoka Tetsumasa、Ujiie Hideyuki、Nishie Wataru、Iwata Hiroaki、Ishikawa Makoto、Higashino Hiroshi、Natsuga Ken、Shinkuma Satoru、Shimizu Hiroshi
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 138 Issue: 6 Pages: 1260-1267

    • DOI

      10.1016/j.jid.2018.01.005

    • NAID

      120006636167

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Epidermal aspects of type VII collagen: Implications for dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita2018

    • Author(s)
      Watanabe Mika、Natsuga Ken、Shinkuma Satoru、Shimizu Hiroshi
    • Journal Title

      The Journal of Dermatology

      Volume: 45 Issue: 5 Pages: 515-521

    • DOI

      10.1111/1346-8138.14222

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Oral mucosa is a useful substrate for detecting autoantibodies of mucous membrane pemphigoid.2018

    • Author(s)
      Kamaguchi M, Iwata H, Ujiie H, Izumi K, Natsuga K, Nishie W, Asaka T, Kitagawa Y, Shimizu H.
    • Journal Title

      Br J Dermatol.

      Volume: 178 Issue: 2 Pages: e119-e121

    • DOI

      10.1111/bjd.15925

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Life before and beyond blistering: The role of collagen XVII in epidermal physiology2018

    • Author(s)
      Natsuga K, Watanabe M, Nishie W, Shimizu H
    • Journal Title

      Exp Dermatol

      Volume: 印刷中 Issue: 10 Pages: 1135-1141

    • DOI

      10.1111/exd.13550

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Acute vascular reaction due to lipo-prostaglandin E12018

    • Author(s)
      Fujimura Y, Watanabe M, Natsuga K, Shimizu H
    • Journal Title

      J Eur Acad Dermatol Venereol

      Volume: 印刷中 Issue: 7

    • DOI

      10.1111/jdv.14807

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Sweet's Syndrome Mimicking Anti-Neutrophil Cytoplasmic Antibodies-Associated Vasculitis2018

    • Author(s)
      Kosumi H, Watanabe M, Natsuga K, Miyauchi T, Shiiya C, Ujiie H, Shimizu H
    • Journal Title

      Am J Med

      Volume: 印刷中 Issue: 6 Pages: e241-e242

    • DOI

      10.1016/j.amjmed.2017.12.033

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Portable negative-pressure wound therapy for pyoderma gangrenosum: Report of two cases2018

    • Author(s)
      Yamaguchi Y, Yanagi T, Sato K, Yoshimoto N, Hirata Y, Ujiie I, Nishimura M, Natsuga K, Shiiya C, Tsukinaga I, Shimizu H
    • Journal Title

      J Dermatol

      Volume: 印刷中 Issue: 4 Pages: 483-486

    • DOI

      10.1111/1346-8138.14180

    • NAID

      120006600950

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Extensive Eruptive Syringoma After Liver Transplantation2018

    • Author(s)
      Maeda T、Natsuga K、Nishie W、Yamashita K、Shimizu H
    • Journal Title

      Acta Derm Venereol

      Volume: 98 Issue: 1 Pages: 119-120

    • DOI

      10.2340/00015555-2814

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss of interaction between plectin and type XVII collagen results in epidermolysis bullosa simplex2017

    • Author(s)
      Natsuga K, Nishie W, Nishimura M, Shinkuma S, Watanabe M, Izumi K, Nakamura H, Hirako Y, Shimizu H
    • Journal Title

      Hum Mutat

      Volume: 38 Issue: 12 Pages: 1666-1670

    • DOI

      10.1002/humu.23344

    • NAID

      120006540047

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] C-Terminal Processing of Collagen XVII Induces Neoepitopes for Linear IgA Dermatosis Autoantibodies2017

    • Author(s)
      Toyonaga Ellen、Nishie Wataru、Izumi Kentaro、Natsuga Ken、Ujiie Hideyuki、Iwata Hiroaki、Yamagami Jun、Hirako Yoshiaki、Sawamura Daisuke、Fujimoto Wataru、Shimizu Hiroshi
    • Journal Title

      Journal of Investigative Dermatology

      Volume: 137 Issue: 12 Pages: 2552-2559

    • DOI

      10.1016/j.jid.2017.07.831

    • NAID

      120006540048

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of mucous membrane pemphigoid autoantibodies by full-length BP180 enzyme-linked immunosorbent assay2017

    • Author(s)
      Izumi Kentaro、Nishie Wataru、Mai Yosuke、Ujiie Hideyuki、Iwata Hiroaki、Natsuga Ken、Shimizu Hiroshi
    • Journal Title

      J Dermatol Sci

      Volume: 88 Issue: 2 Pages: 247-248

    • DOI

      10.1016/j.jdermsci.2017.07.005

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Appearance of antidesmocollin 1 autoantibodies leading to a vegetative lesion in a patient with pemphigus vulgaris2017

    • Author(s)
      Yamaguchi Y.、Shinkuma S.、Ishii N.、Takashima S.、Natsuga K.、Ujiie H.、Iwata H.、Nomura T.、Fujita Y.、Hamasaka A.、Hamasaka K.、Hashimoto T.、Shimizu H.
    • Journal Title

      Br J Dermatol

      Volume: 178 Issue: 1 Pages: 294-295

    • DOI

      10.1111/bjd.15834

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Type XVII collagen coordinates proliferation in the interfollicular epidermis.2017

    • Author(s)
      Watanabe M, Natsuga K, Nishie W, Kobayashi Y, Donati G, Suzuk Si, Fujimura Y, Tsukiyama T, Ujiie H, Shinkuma S, Nakamura H, Murakami M, Ozaki M, Nagayama M, Watt F and Shimizu H
    • Journal Title

      eLife

      Volume: 6:e26635 Pages: 1-24

    • DOI

      10.7554/elife.26635

    • NAID

      120006337772

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cutis Verticis Gyrata Fluctuation with Atopic Dermatitis Disease Activity2017

    • Author(s)
      Kosumi H、Izumi K、Natsuga K、Yamaguchi Y、Itami A、Shimizu H
    • Journal Title

      Acta Derm Venereol

      Volume: 97 Issue: 10 Pages: 1245-1246

    • DOI

      10.2340/00015555-2750

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generalized Pustular Psoriasis2017

    • Author(s)
      Kosumi Hideyuki、Ito Takamasa、Fujita Yasuyuki、Izumi Kentaro、Maya Yuka、Yanagi Teruki、Natsuga Ken、Ujiie Hideyuki、Shinkuma Satoru、Nomura Toshifumi、Sadanobu Naoya、Shimizu Hiroshi
    • Journal Title

      J Pediatr

      Volume: 188 Pages: 305-305.e1

    • DOI

      10.1016/j.jpeds.2017.05.058

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] A case of recessive dystrophic epidermolysis bullosa with a novel c.6885_6898del14 mutation in the COL7A1 gene2017

    • Author(s)
      Shinkuma S, Masunaga T, Miyawaki S, Takashima S, Natsuga K, Nomura T, Fujita Y, Nakamura H, Shimizu H
    • Journal Title

      J Dermatol Sci

      Volume: 88 Issue: 1 Pages: 139-141

    • DOI

      10.1016/j.jdermsci.2017.03.022

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Autoantibodies of non-inflammatory bullous pemphigoid hardly deplete type XVII collagen of keratinocytes2017

    • Author(s)
      Imafuku K, Iwata H, Kamaguchi M, Izumi K, Natsuga K, Ujiie H, Nishie W, Shimizu H
    • Journal Title

      Exp Dermatol

      Volume: 印刷中 Issue: 12 Pages: 1171-1174

    • DOI

      10.1111/exd.13331

    • NAID

      120006540054

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Psoriasiform mycosis fungoides masquerading as tumourous plaques2017

    • Author(s)
      Yamaguchi Y, Fujita Y, Hirata Y, Nishimura M, Shinkuma S, Natsuga K, Hida T, Kato N, Shimizu H
    • Journal Title

      Eur J Dermatol

      Volume: 印刷中 Issue: 3 Pages: 295-296

    • DOI

      10.1684/ejd.2017.2971

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 表皮の恒常性維持と外的刺激に対する応答2019

    • Author(s)
      夏賀 健
    • Organizer
      第1回炎症性皮膚疾患集中セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Clavus serves as a model of epidermal stem cell responses to mechanical forces2018

    • Author(s)
      Natsuga K, Watanabe M, Hata H, Kobayashi Y, Nagayama M, Shimizu H
    • Organizer
      International Investigative Dermatology 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Organization of the epidermal basement membrane zone determined through super-resolution microscopy2018

    • Author(s)
      Natsuga K, Watanabe M, Shimizu H
    • Organizer
      7th SSSR and SCUR meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 表皮化水疱症 発症機序/新規治療法の最新の進歩2018

    • Author(s)
      夏賀 健
    • Organizer
      第117回日本皮膚科学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Abnormalities in laminin-332 have post-translational effects on laminin γ22017

    • Author(s)
      Natsuga K, Nishie W, Watanabe M, Nakamura H, Shinkuma S, Shimizu H
    • Organizer
      EB2017 - 5th World Conference of EB Research & 4th Conference of EB-CLINET
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2020-03-30  

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