The effect of trichostatin A, one of the histone deacetylaseinhibitor, on skin fibrosis of systemic sclerosis mouse model

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591245
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Dermatology
• Research Institution: Nagasaki University
• Principal Investigator: OGAWA Fumihide 長崎大学, 大学病院, 講師 (10333519)
• Co-Investigator(Kenkyū-buntansha): SHIMIZU Kazuhiro 長崎大学, 大学院・医歯薬学総合研究科, 准教 (80170968) ; SATO Shinichi 東京大学, 医学部附属病院, 教授 (20215792)
• Project Period (FY): 2010 – 2012
• Keywords: 強皮症 / 膚硬化 / ストン脱アセチル化酵素 / モデルマウス / トリコスタチンA

Research Abstract

Systemic sclerosis (SSc) is connective tissue disorder characterized by severe fibrosis of the skin and various internal organs. Tight skin (TSK/+) mouse is a putative murine model of SSc characterized by excessive collagen deposition in skin. Bleomycin-induced SSc model mouse, which is another model of SSc, is established using subcutaneous bleomycin treatment. TSA was injected subcutaneously into the back of the TSK/+, bleomycin-induced SSc model mice, and wild type mice. TSA significantly decreased the development of TSK mouse skin fibrosis by reducing the hypodermal thickness. Furthermore, skin mRNA expressions of type I collagen and fibrogenic cytokines were markedly attenuated by TSA administration. However, TSA could not decrease the skin sclerosis of bleomycin-induced SSc model. These results suggest that TSA decreases skin fibrosis only in TSK mouse by regulating expression of collagen and fibrogenic cytokines and does not affect systemic immune level. The effect of TSA for skin sclerosis may depend on the pathogenesis of sclerosis.

Research Products

• [Journal Article] Autoantibodies to small ubiquitin-like modifier activating enzymes in Japanese patients with dermatomyositis: comparison with a UK Caucasian cohort (2013)
  • Author(s): Fujimoto M, Matsushita T, Hamaguchi Y, Kaji K, Asano Y, Ogawa F, Yamaoka T, Fujikawa K, Tsukada T, Sato K, Echigo T, Hasegawa M, Takehara K
  • Journal Title: Ann Rheum Dis Volume: 72(1) Pages: 151-153
  • Peer Reviewed
• [Journal Article] Exogenous application of hydrogen sulfide donor attenuates inflammatory reactions through L-selectin involved pathway in the cutaneous reverse passive Arthus reaction (2013)
  • Author(s): Shimizu K, Ogawa F, Hara T, Yoshizaki A, Muroi E, Akiyama Y, Yanaba K, Yamaoka T, Sato S
  • Journal Title: J Leukoc Biol: accepted
  • Peer Reviewed
• [Journal Article] Myositis-specific anti-155/140 autoantibodies target transcription intermediary factor 1 family proteins (2012)
  • Author(s): Fujimoto M, Hamaguchi Y, Kaji K, Matsushita T, Ichimura Y, Kodera M, Ishiguro N, Ueda-Hayakawa I, Asano Y, Ogawa F, Fujikawa K, Miyagi T, Mabuchi E, Hirose K, Akimoto N, Hatta N, Tsutsui K, Higashi A, Igarashi A, Seishima M, Hasegawa M, Takehara K
  • Journal Title: Arthritis Rheum Volume: 64(2) Pages: 513-522
  • Peer Reviewed
• [Journal Article] Periorbital milia-like calcinosis (2012)
  • Author(s): Tomita H, Ogawa F, Yoshizaki A, Akiyama Y, Kinoshita N, Utani A
  • Journal Title: Clin Exp Dermatol Volume: 37(7) Pages: 787-788
  • Peer Reviewed
• [Journal Article] Increased serum levels of soluble CD163 in patients with scleroderma (2012)
  • Author(s): Shimizu K, Ogawa F, Yoshizaki A, Akiyama Y, Kuwatsuka Y, Okazaki S, Tomita H, Takenaka M, Sato S
  • Journal Title: Clin Rheumatol Volume: 31(7) Pages: 1059-1064
  • Peer Reviewed
• [Journal Article] Investigation of prognostic factors for skin sclerosis and lung function in Japanese patients with early systemic sclerosis: a multicentre prospective observational stud (2012)
  • Author(s): Hasegawa M, Asano Y, Endo H, Fujimoto M, Goto D, Ihn H, Inoue K, Ishikawa O, Kawaguchi Y, Kuwana M, Muro Y, Ogawa F, Sasaki T, Takahashi H, Tanaka S, Takehara K, Sato S
  • Journal Title: Rheumatology (Oxford) Volume: 51(1) Pages: 129-133
  • Peer Reviewed
• [Presentation] The effect of trichostatin a, one of the histone deacetylase inhibitor, on skin fibrosis mouse. (2011)
  • Author(s): Ogawa F, Tomita H, Kuwatsuka Y, Shimizu K, Sato S, Utani A
  • Organizer: 2011 ACR 75th/ARHP 46th Annual Scientific Meeting
  • Place of Presentation: Chicago, USA
  • Year and Date: 20111104-09