• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Significance of kallikrein-5 in the formation of filaggrin monomer

Research Project

Project/Area Number 24659525
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Dermatology
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

TOKURA Yoshiki  浜松医科大学, 医学部, 教授 (00172156)

Co-Investigator(Kenkyū-buntansha) HIRAKAWA Satoshi  浜松医科大学, 医学部, 准教授 (50419511)
Co-Investigator(Renkei-kenkyūsha) SAKAVE Jun-ichi  浜松医科大学, 医学部, 特任助教 (30631494)
Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords皮膚生理学 / フィラグリン / 角層 / バリア / カリクレイン / 角化細胞 / 皮膚バリア / アトピー性皮膚炎 / プロフィラグリン
Research Abstract

Filaggrin contributes to the formation of the human skin barrier. Profilaggrin is cleaved by proteolytic enzymes and converted to functional filaggrin, but its processing mechanism remains not fully elucidated. Kallikrein-related peptidase 5 (KLK5) is a major serine protease found in the skin. We searched for profilaggrin-processing protease(s) by partial purification of epidermal extracts and found KLK5 as a possible candidate. We used HPLC coupled with mass spectrometry to show that KLK5 cleaves profilaggrin. KLK5 also cleaved fusion protein containing liker of profilaggrin. Furthermore, based on a proximity ligation assay, immunohistochemistry, and immunoelectron microscopy analysis, we reveal that KLK5 and profilaggrin co-localize in the stratum granulosum in human epidermis. KLK5 knockdown in normal cultured human epidermal keratinocytes resulted in higher levels of profilaggrin, indicating that KLK5 potentially functions in profilaggrin cleavage.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (26 results)

All 2014 2013 2012 Other

All Journal Article (10 results) (of which Peer Reviewed: 5 results) Presentation (8 results) (of which Invited: 2 results) Book (6 results) Remarks (2 results)

  • [Journal Article] Atopic dermatitis presenting as generalized poikiloderma with filaggrin gene mutation2014

    • Author(s)
      Nakazawa S, Moriki M, Ikeya S, Sakabe J-I, Tokura Y
    • Journal Title

      J Dermatol

      Volume: 印刷中

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kallikrein-related peptidase 5 functions in proteolytic processing of profilaggrin in cultured human keratinocytes2013

    • Author(s)
      Sakabe J, Yamamoto M, Hirakawa S, Motoyama A, Ohta I, Tatsuno K, Ito T, Kabashima K, Hibino T, Tokura Y.
    • Journal Title

      J Biol Chem

      Volume: 288 Pages: 17179-17189

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Journal Article] High frequencies of positive nickel/cobalt patch tests and high sweat nickel concentration in patients with intrinsic atopic dermatitis2013

    • Author(s)
      Yamaguchi H, Kabashima-Kubo R, Bito T, Sakabe JI, Shimauchi T, Ito T, Hirakawa S, Hirasawa N, Ogasawara K, Tokura Y.
    • Journal Title

      J Dermatol Sci

      Volume: 72(3) Pages: 240-245

    • Related Report
      2013 Final Research Report
  • [Journal Article] Second report of FLG R501X mutation in Japanese patients with atopic dermatitis2013

    • Author(s)
      Yamaguchi H, Tatsuno K, Sakabe J, Tokura Y.
    • Journal Title

      J Dermatol

      Volume: 40 Pages: 498-499

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Journal Article] High frequencies of positive nickel/cobalt patch tests and high sweat nickel concentration in patients with intrinsic atopic dermatitis.2013

    • Author(s)
      Yamaguchi H, Kabashima-Kubo R, Bito T, Sakabe JI, Shimauchi T, Ito T, Hirakawa S, Hirasawa N, Ogasawara K, Tokura Y
    • Journal Title

      J Dermatol Sci

      Volume: 73 Issue: 3 Pages: 240-245

    • DOI

      10.1016/j.jdermsci.2013.07.009

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Second report of FLG R501X mutation in Japanese patients with atopic dermatitis.2013

    • Author(s)
      Yamaguchi H, Tatsuno K, Sakabe J, Tokura Y
    • Journal Title

      J Dermatol

      Volume: in press Issue: 6 Pages: 498-499

    • DOI

      10.1111/1346-8138.12133

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency : Possible immunological state of the intrinsic type2012

    • Author(s)
      Kabashima-Kubo R, Nakamura M, Sakabe JI, Sugita K, Hino R, Mori T, Kobayashi M, Bito T, Kabashima K, Ogasawara K, Nomura Y, Nomura T, Akiyama M, Shimizu H, Tokura Y.
    • Journal Title

      J Dermatol Sci

      Volume: 67 Pages: 37-43

    • Related Report
      2013 Final Research Report
  • [Journal Article] A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency: Possible immunological state of the intrinsic type2012

    • Author(s)
      Kabashima-Kubo R, Nakamura M, Sakabe, J, Sigita K, Hino R, Mori T, Kobayashi M, Bito T, Kabashima K, Ogasawara K, Nomura Y, Nomura T, Akiyama M, Shimizu H, Tokura Y.
    • Journal Title

      J Dermatol Sci

      Volume: 67 Issue: 1 Pages: 37-43

    • DOI

      10.1016/j.jdermsci.2012.04.004

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Defective epidermal innate immunity and resultant superficial dermatophytosis in adult T-cell leukemia/lymphoma2012

    • Author(s)
      Sawada Y
    • Journal Title

      Clin Cancer Res

      Volume: 18 Issue: 14 Pages: 3772-3779

    • DOI

      10.1158/1078-0432.ccr-12-0292

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Atopic dermatitis presenting as generalized poikiloderma with filaggrin gene mutation

    • Author(s)
      Nakazawa S, Moriki M, Ikeya S, Sakabe J-I, Tokura Y.
    • Journal Title

      J Dermatol

      Volume: (in press)

    • Related Report
      2013 Final Research Report
  • [Presentation] Proteome analysis of corneum from atopic dermatitis patients2014

    • Author(s)
      Tokura Y.
    • Organizer
      World Rendez-vous on Dermatology
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2014-03-11
    • Related Report
      2013 Final Research Report
  • [Presentation] Profilaggrin processing and metal allergy : Novel aspects of atopic dermatitis2013

    • Author(s)
      Tokura Y.
    • Organizer
      International Immunodermatology Symposium(Post-IID 2013)
    • Place of Presentation
      Heidelberg, Germany
    • Year and Date
      2013-05-13
    • Related Report
      2013 Final Research Report
  • [Presentation] Involvement of kallikrein-related peptidase 5 in profilaggrin processing2013

    • Author(s)
      Sakabe J, Yamamoto M, Motoyama A, Ohta I, Hirakawa S, Hibino T, Tokura Y.
    • Organizer
      2013 International Investigative Dermatology Meeting
    • Place of Presentation
      Edinburgh, United Kingdom
    • Related Report
      2013 Final Research Report
  • [Presentation] Involvement of kallikrein-related peptidase 5 in profilaggrin processing2013

    • Author(s)
      Sakabe J, Yamamoto M, Motoyama A, Ohta I, Hirakawa S, Hibino T, Tokura Y
    • Organizer
      International Investigative Dermatology
    • Place of Presentation
      英国 エディンバラ
    • Related Report
      2013 Annual Research Report
  • [Presentation] Co-localization of kallikrein5 and profilaggrin in keratohyalin granules and reduction of filaggrin monomers by kallikrein5 downmodulation2012

    • Author(s)
      Sakabe J, Ohta I, Hirakawa S, Tokura Y.
    • Organizer
      The 37th Annual Meeting of the Japanese Society for Investigative Dermatology
    • Place of Presentation
      Naha, Japan
    • Related Report
      2013 Final Research Report
  • [Presentation] Profilaggrin processing and metal allergy: Novel aspects of atopic dermatitis

    • Author(s)
      Tokura Y
    • Organizer
      International Immunodermatology Symposium (Post-IID 2013)
    • Place of Presentation
      独国 ハイデルベルク
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Innate immunity of the epidermis toward bacterial and fungal infection : lessons from Th17-dysregulated conditions.

    • Author(s)
      Tokura Y
    • Organizer
      The 10th Symposium of the Cutaneous Biology Research Institute
    • Place of Presentation
      韓国 ソウル
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Co-localization of kallikrein5 and profilaggrin in keratohyalin granules and reduction of filaggrin monomers by kallikrein5 downmodulation.

    • Author(s)
      Sakabe J, Ohta I, Hirakawa S, Tokura Y
    • Organizer
      The 37th Annual Meeting of the Japanese Society for Investigative Dermatology.
    • Place of Presentation
      沖縄
    • Related Report
      2012 Research-status Report
  • [Book] アトピー性皮膚炎:皮膚バリアの破綻によるアレルギー.実験医学312013

    • Author(s)
      戸倉新樹
    • Related Report
      2013 Final Research Report
  • [Book] フィラグリン異常とアレルギー疾患の進展.モダンフィジジャン332013

    • Author(s)
      戸倉新樹
    • Related Report
      2013 Final Research Report
  • [Book] 実験医学2013

    • Author(s)
      戸倉新樹
    • Total Pages
      7
    • Publisher
      羊土社
    • Related Report
      2013 Annual Research Report
  • [Book] IgE 値正常の内因性アトピー性皮膚炎の成因は如何に.皮膚アレルギーフロンティア.102012

    • Author(s)
      戸倉新樹
    • Related Report
      2013 Final Research Report
  • [Book] 皮膚バリアからみるアトピー性皮膚炎の全体像.臨床免疫・アレルギー科582012

    • Author(s)
      戸倉新樹
    • Related Report
      2013 Final Research Report
  • [Book] 1冊でわかる皮膚アレルギー2012

    • Author(s)
      戸倉新樹
    • Total Pages
      2
    • Publisher
      文光堂
    • Related Report
      2012 Research-status Report
  • [Remarks] 浜松医科大学皮膚科学講座業績

    • URL

      http://www2.hama-med.ac.jp/w1b/derm/achievements/index.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 浜松医科大学皮膚科学講座 業績

    • URL

      http://www2.hama-med.ac.jp/w1b/derm/achievements/index.html

    • Related Report
      2013 Annual Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi