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A molecular study on skin barrier dysfunction in atopic dermatitis

Research Project

Project/Area Number 24248055
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Clinical veterinary science
Research InstitutionTokyo University of Agriculture and Technology

Principal Investigator

MATSUDA Hiroshi  東京農工大学, (連合)農学研究科(研究院), 教授 (80145820)

Co-Investigator(Kenkyū-buntansha) TANAKA Akane  東京農工大学, 大学院農学研究院, 教授 (80418673)
OHMORI Keitaro  東京農工大学, 大学院農学研究院, 講師 (20466915)
MATSUDA Akira  東京農工大学, 大学院農学研究院, 助教 (90613969)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥32,370,000 (Direct Cost: ¥24,900,000、Indirect Cost: ¥7,470,000)
Fiscal Year 2014: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Fiscal Year 2013: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2012: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Keywordsトランスレーショナルリサーチ / 動物 / 酵素 / ストレス
Outline of Final Research Achievements

Raised skin pH may result in enzymatic activation of kallikrein 5 (KLK5), a serine protease thought to play a crucial role in skin barrier destruction. Although skin surface pH is increased in patients with atopic dermatitis (AD), contribution of pH to initiation of AD has been unclear. By using NC/Tnd mice, a model for human AD, skin pH and transepidermal water loss (TEWL), as well as KLK5, protease-activated receptor 2 (PAR2), and thymic stromal lymphopoietin (TSLP) were measured. Acidification of the skin reduced KLK5 activity in the epidermis and ameliorated the eczema. In contrast, alkalization of the skin increased epidermal expression of KLK5 and TEWL, resulting in development of AD, even in SPF NC/Tnd mice without AD. Skin surface pH modulates KLK5 production, which might directly be responsible for barrier dysfunction, itch sensation, and allergic inflammation by activating a PAR2 and TSLP cascade in the epidermis.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (30 results)

All 2015 2014 2013 2012 Other

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (15 results) (of which Invited: 4 results) Remarks (3 results)

  • [Journal Article] Dihomo-γ-linolenic acid prevents the development of atopic dermatitis through prostaglandin D1 production in NC/Tnd mice.2015

    • Author(s)
      Amagai Y, Oida K, Matsuda A, Jung K, Kakutani S, Tanaka T, Matsuda K, Jang H, Ahn G, Xia Y, Kawashima H, Shibata H, Matsuda H, Tanaka A.
    • Journal Title

      J. Dermatol. Sci.

      Volume: In press Issue: 1 Pages: 30-37

    • DOI

      10.1016/j.jdermsci.2015.03.010

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Ultra-pure Soft Water Ameliorates Atopic Skin Disease by Preventing Metallic Soap Deposition in NC/Tnd Mice and Reduces Skin Dryness in Humans.2015

    • Author(s)
      Tanaka A, Matsuda A, Jung K, Jang H, Ahn G, Ishizaka S, Amagai Y, Oida K, Arkwright PD, Matsuda H.
    • Journal Title

      Acta Derm Venereol.

      Volume: In press Pages: 787-791

    • DOI

      10.2340/00015555-2083

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Ultra-pure soft water improves skin barrier function in children with atopic dermatitis: a randomized, double-blind, placebo-controlled, crossover pilot study.2014

    • Author(s)
      Togawa Y, Kambe N, Shimojo N, Nakano T, Sato Y, Mochizuki H, Tanaka A, Matsuda H, Matsue H.
    • Journal Title

      J. Dermatol. Sci.

      Volume: 76 Issue: 3 Pages: 269-271

    • DOI

      10.1016/j.jdermsci.2014.10.009

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppressive effect of mangosteen rind extract on the spontaneous development of atopic dermatitis in NC/Tnd mice.2013

    • Author(s)
      Higuchi H, Tanaka A, Nishikawa S, Oida K, Matsuda A, Jung K, Amagai Y, Matsuda H.
    • Journal Title

      Jounal of Dermatology

      Volume: 40 Issue: 10 Pages: 786-796

    • DOI

      10.1111/1346-8138.12250

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased expression of gelatinase and caspase activities in the skin of NC/Tnd mice: a model for atopic dermatitis.2013

    • Author(s)
      Kobayashi T, Hayakawa K, Tanaka A, Matsuda H.
    • Journal Title

      Dermatitis

      Volume: 24 Issue: 5 Pages: 254-255

    • DOI

      10.1097/der.0b013e31829f2895

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Topical application of ketoprofen improves gait disturbance in rat models of acute inflammation.2013

    • Author(s)
      Amagai Y, Tanaka A, Matsuda A, Oida K, Jung K, Nishikawa S, Jang H, Ishizaka S, Matsuda H.
    • Journal Title

      Biomed Research International

      Volume: 2013 Pages: 540231-540231

    • DOI

      10.1155/2013/540231

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Abnormalities in itch sensation and skin barrier function in atopic NC/Tnd mice.2013

    • Author(s)
      Amagai Y, Matsuda H, Tanaka A.
    • Journal Title

      Biology and Pharmacology Bullen

      Volume: 36 Pages: 1248-1252

    • NAID

      130003361501

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Daily intake of Jeju groundwater improves the skin condition of the model mouse for human atopic dermatitis.2013

    • Author(s)
      Tanaka A, Jung K, Matsuda A, Jang H, Kajiwara N, Amagai Y, Oida K, Ahn G, Ohmori K, Kang KG, Matsuda H
    • Journal Title

      Journal of Dermatology

      Volume: 40 Issue: 3 Pages: 193-200

    • DOI

      10.1111/1346-8138.12055

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heterogeneity of internal tandem duplications in the c-kit of dogs with multiple mast cell tumors2013

    • Author(s)
      Amagai Y, Akane T, Matsuda A, Oida K, Jung K, Nishikawa S, Jang H, Matsuda H
    • Journal Title

      J. Small Anim. Prac

      Volume: (In press) Issue: 7 Pages: 377-380

    • DOI

      10.1111/jsap.12069

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Supplementation of the fermented soy product ImmuBalanceTM effectively reduces itching behavior of atopic NC/Tnd mice2012

    • Author(s)
      Matsuda A, Tanaka A, Pan W, Okamoto N, Oida K, Kingyo N, Amagai Y, Xia Y, Jang H, Nishikawa S, Kajiwara N, Ahn G, Ohmori K, Matsuda H
    • Journal Title

      J. Dermatol. Sci

      Volume: 67(2) Issue: 2 Pages: 130-139

    • DOI

      10.1016/j.jdermsci.2012.05.011

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recent findings in mouse models for human atopic dermatitis.2012

    • Author(s)
      Tanaka A, Amagai Y, Oida K, Matsuda H.
    • Journal Title

      Experimental Animals

      Volume: 61 Pages: 77-84

    • NAID

      10030555601

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The JNK/NFκB pathway is required to activate murine lymphocytes induced by a sulfated polysaccharide from Ecklonia cava2012

    • Author(s)
      Ahn G, Bing SJ, Kang SM, Lee WW, Lee SH, Matsuda H, Tanaka A, Cho IH, Jeon YJ, Jee Y
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1830 Issue: 3 Pages: 2820-2829

    • DOI

      10.1016/j.bbagen.2012.12.008

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] アトピー性皮膚炎の新しい治療戦略ー高純度軟化水による皮膚バリア修復ー2015

    • Author(s)
      松田浩珍
    • Organizer
      第45回日本比較臨床医学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2015-03-01
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Involvement of skin surface on development of atopic dermatitis2014

    • Author(s)
      Jang H, Tanaka A, Matsuda H
    • Organizer
      The 39th Annual Meeting of the Japanese Scociety for Investigative Dermatology
    • Place of Presentation
      大阪
    • Year and Date
      2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Relevance between skin condition and itch during development of atopic dermatitis2014

    • Author(s)
      Tanaka A, Jang H, Matsuda H
    • Organizer
      24th International Symposium of Itch
    • Place of Presentation
      東京
    • Year and Date
      2014-10-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 皮膚pHの変化と皮膚バリア損傷との関連2014

    • Author(s)
      張孝善、田中あかね、松田浩珍
    • Organizer
      第157回日本獣医学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2014-09-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] Involvement of skin surface pH on barrier function in development of atopic dermatitis2014

    • Author(s)
      Jang H, Tanaka A, Matsuda H
    • Organizer
      European Academy of Allergy and Clinical Immunology Congress
    • Place of Presentation
      デンマーク、コペンハーゲン
    • Year and Date
      2014-06-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] アトピー性皮膚炎治療における皮膚pH調節の重要性

    • Author(s)
      張孝善、田中あかね、松田彬、松田浩珍
    • Organizer
      第156回日本獣医学会学術集会
    • Place of Presentation
      岐阜、岐阜大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] カジメに含まれるdieckolのアトピー性皮膚炎症状に対する治療効果

    • Author(s)
      安キンネ、田中あかね、松田彬、松田浩珍
    • Organizer
      第156回日本獣医学会学術集会
    • Place of Presentation
      岐阜、岐阜大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] アトピー性皮膚炎の皮膚におけるHIF-1αの発現について

    • Author(s)
      南出夏奈、田中あかね、松田彬、松田浩珍
    • Organizer
      第156回日本獣医学会学術集会
    • Place of Presentation
      岐阜、岐阜大学
    • Related Report
      2013 Annual Research Report
  • [Presentation] Influence of the potential hydrogen on skin barrier function and immune responses in NC/Tnd mice, a model for human AD

    • Author(s)
      Jang H, Tanaka A, Matsuda A, Matsuda H.
    • Organizer
      欧州臨床免疫アレルギー学会
    • Place of Presentation
      イタリア、ミラノ
    • Related Report
      2013 Annual Research Report
  • [Presentation] House dust mite allergens induce IgE-independent activation of canine mast cells NI-1

    • Author(s)
      Oida K, Tanaka A, Matsuda H, Jensen-Jarolim E.
    • Organizer
      欧州臨床免疫アレルギー学会
    • Place of Presentation
      イタリア、ミラノ
    • Related Report
      2013 Annual Research Report
  • [Presentation] モーションキャプチャーによるバイオマーカーの探索

    • Author(s)
      松田浩珍
    • Organizer
      第5回レドックス・ライフイノベーションシンポジウム
    • Place of Presentation
      東京・東京フォーラム
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Key factors for success in industry-university collaboration

    • Author(s)
      Hiroshi Matsuda
    • Organizer
      AUTM 2013 Annual Meeting
    • Place of Presentation
      USA・SanAntonio Convention Center
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Involvment of daily metallic soap in skin conditions of patients with atopic dermatitis

    • Author(s)
      Akane Tanaka, Hiroshi Matsuda, et al.
    • Organizer
      EAACI Skin Allergy Meeting 2012
    • Place of Presentation
      Germany・Berlin Convention Hall
    • Related Report
      2012 Annual Research Report
  • [Presentation] Pain sensitivity in NC/Tnd mice with atopic dermatitis

    • Author(s)
      Yan Xia, Akane Tanaka, Hiroshi Matsuda, et al.
    • Organizer
      22nd International Symposium of Itch
    • Place of Presentation
      Tokyo・Belle Salle Jinbocho
    • Related Report
      2012 Annual Research Report
  • [Presentation] アトピー性皮膚炎モデルマウスにおける皮膚pHと皮膚バリア損傷の関連性

    • Author(s)
      Hyuson Jang, Akane Tanaka, Hiroshi Matsuda, et al.
    • Organizer
      日本獣医学会
    • Place of Presentation
      岩手県盛岡市・岩手大学
    • Related Report
      2012 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.tuat.ac.jp/~mol_path/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.tuat.ac.jp/~mol_path/

    • Related Report
      2013 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.tuat.ac.jp/~mol_path/

    • Related Report
      2012 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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