Serine proteinase dysfunction in keratinocyte of Papillon-Lefevre syndrome

2011 Fiscal Year Final Research Report

• Project/Area Number: 22791048
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Dermatology
• Research Institution: Hirosaki University
• Principal Investigator: TAKIYOSHI Noriko 弘前大学, 医学部・附属病院, 助手 (30568895)
• Project Period (FY): 2010 – 2011
• Keywords: 過角化 / 遺伝子変異 / 癌 / 表皮細胞 / メラノサイト

Research Abstract

Papillon-Lefevre syndrome (PLS) is characterized by palmoplantar keratosis (PPK) and early-onset periodontitis, caused by deficiency of cathepsin C (CTSC) that activates many serine proteinases. The pathogenesis of PPK in PLS has not been determined. We confirmed that CTSC activates Kallikrein 8 (KLK8) in immortal human keratinocyte line ; HaCaT cell, by stimulating with recombinant CTSC. KLK8 is one of serine proteinase, and has been reported that plays a role in shedding the corneocytes. Furthermore, histopathological finding showed that topical TPA application caused significant hyperkeratosis in the epidermis of CTSC knockout mice, compared to wild type. These findings suggest that an absence of CTSC causes a serine proteinase dysfunction, leads to hyperkeratosis in the epidermi.

Research Products

• [Journal Article] Buschke-Ollendorff syndrome associated with hypertrophic scar formation : a possible role for LEMD3 mutation (2012)
  • Author(s): Korekawa A, Nakano H, Toyomaki Y, Takiyoshi N, Rokunohe D, Akasaka E, Nakajima K, Sawamura D
  • Journal Title: Br J Dermatol Volume: 166 Pages: 900-903
  • DOI: DOI:10.1111/j.1365-2133.2011.10691.x.
  • Peer Reviewed
• [Journal Article] Epidermolysis bullosa pruriginosa with marked phenotypic heterogeneity caused by a recurrent glycine substitution : incomplete penetrance or a latent case? (2011)
  • Author(s): Takiyoshi N, Nakano H, Sawamura D
  • Journal Title: J Dermatol
  • Peer Reviewed
• [Journal Article] Diffuse and focal palmoplantar keratoderma can be caused by a keratin 6c mutation (2011)
  • Author(s): Akasaka E, Nakano H, Nakano A, Toyomaki Y, Takiyoshi N, Rokunohe D, Nishikawa Y, Korekawa A, Matsuzaki Y, Mitsuhashi Y, Sawamura D
  • Journal Title: Br J Dermatol Volume: 165(6) Pages: 1290-1292
  • DOI: DOI:10.1111/j.1365-2133.2011.10552.x.
  • Peer Reviewed
• [Presentation] Functional analyses in Papillon-Lefevre syndrome (2011)
  • Author(s): 滝吉典子
  • Organizer: 日本研究皮膚科学会第36回年次学術大会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2011-12-10
• [Presentation] Mutational analyses in Papillon-Lefevre syndrome (2011)
  • Author(s): Takiyoshi Noriko
  • Organizer: The 41st Annual Meeting of the European Society for Dermatological Research (ESDR)
  • Place of Presentation: バルセロナ(スペイン)
  • Year and Date: 2011-09-09
• [Presentation] カテプシンC遺伝子変異が同定されたPapillon-Lefevre症候群の2家系 (2011)
  • Author(s): 滝吉典子
  • Organizer: 第26回角化症研究会
  • Place of Presentation: 東京商工会議所
  • Year and Date: 2011-07-30
• [Presentation] カテプシンC遺伝子変異が同定されたPapillon-Lefevre症候群の1家系の報告及び、ケラチノサイト由来細胞におけるカテプシンC発現の検討 (2010)
  • Author(s): 滝吉典子
  • Organizer: 第17回分子皮膚科学フォーラム
  • Place of Presentation: ホテルオークラ福岡(福岡市)
  • Year and Date: 2010-07-10