siRNA for the treatment of airway remodeling

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590859
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Mie University
• Principal Investigator: KOBAYASHI Tetsu 三重大学, 医学部附属病院, 講師 (20437114)
• Co-Investigator(Kenkyū-buntansha): TAGUCHI Osamu 三重大学, 医学系研究科, 准教授 (00293770)
• Project Period (FY): 2010 – 2012
• Keywords: 肺線維症 / siRNA / RNAi / TGF-β / リモデリング

Research Abstract

SiRNA has been the focus of attention for its potential application for the development of new drugs.To evaluate the effect of intratracheal administration of siRNAs in murine disease models. Firstly, bleomycin was used for induction of lung fibrosis. After confirming the effectiveness of siRNA effect in vitro, siRNAs for several targets including TGF-beta1 were intratracheally administered by inhalation. Mice treated with scrambled siRNA or vehicle were used as controls. We generated a novel model of human TGF-beta1 transgenic mouse that spontaneously develops pulmonary fibrosis. Intrapulmonary delivery of aerosolized siRNAs of TGF-beta1 significantly inhibited bleomycin-induced pulmonary fibrosis. In addition, aerosolized siRNAs against human TGF-beta1 also inhibited spontaneous pulmonary fibrosis.These results suggest that intratracheal instillation of RNAi agents may be useful for the therapy of airway remodeling.

Research Products

• [Journal Article] Efficacy of a novel class of RNA interference therapeutic agents (2012)
  • Author(s): Hamasaki T, Suzuki H, Shirohzu H, Matsumoto T, D'Alessandro-Gabazza CN,Gil-Bernabe P, Boveda-Ruiz D, Naito M, Kobayashi T, Toda M, Mizutani T, TaguchiO, Morser J, Eguchi Y, Kuroda M, Ochiya T, Hayashi H, Gabazza EC, Ohgi T
  • Journal Title: PLoS One Volume: 7 Pages: e42655
  • DOI: DOI:10.1371/journal.pone.0042655
  • Peer Reviewed
• [Journal Article] Correlation between circulating fibrocytes, and activity andprogression of interstitial lung diseases (2012)
  • Author(s): Fujiwara A, Kobayashi H, Masuya M, Maruyama M, Nakamura S, Ibata H, FujimotoH, Ohnishi M, Urawa M, Naito M, Takagi T, Kobayashi T, Gabazza EC, Takei Y,Taguchi O
  • Journal Title: Respirology Volume: 17 Pages: 693-8
  • DOI: DOI:10.1111/j.1440-1843.2012.02167.x
  • Peer Reviewed
• [Journal Article] Role of thrombin-activatablefibrinolysis inhibitor in allergic bronchial asthma (2012)
  • Author(s): Fujiwara A, Taguchi O, Takagi T, D'Alessandro-Gabazza CN, Boveda-Ruiz D, Toda M, Yasukawa A, Matsushima Y, Miyake Y, Kobayashi H, Kobayashi T, Gil-Bernabe P,Naito M, Yoshida M, Morser J, Takei Y, Gabazza EC.
  • Journal Title: Lung Volume: 190 Pages: 189-98
  • Peer Reviewed
• [Journal Article] Development and preclinical efficacy of novel transforming growthfactor-β1 short interfering RNAs for pulmonary fibrosis (2012)
  • Author(s): D'Alessandro-Gabazza CN, Kobayashi T, Boveda-Ruiz D, Takagi T, Toda M,Gil-Bernabe P, Miyake Y, Yasukawa A, Matsuda Y, Suzuki N, Saito H, Yano Y, Fukuda A, Hasegawa T, Toyobuku H, Rennard SI, Wagner PD, Morser J, Takei Y, Taguchi O, Gabazza EC
  • Journal Title: Am J Respir Cell MolBiol Volume: 46 Pages: 397-406
  • Peer Reviewed
• [Journal Article] Inhibition of allergicbronchial asthma by thrombomodulin is mediated by dendritic cells (2011)
  • Author(s): Takagi T, Taguchi O, Toda M, Ruiz DB, Bernabe PG, D'Alessandro-Gabazza CN,Miyake Y, Kobayashi T, Aoki S, Chiba F, Yano Y, Conway EM, Munesue S, Yamamoto Y,Yamamoto H, Suzuki K, Takei Y, Morser J, Gabazza EC
  • Journal Title: Am J RespirCrit Care Med Volume: 183 Pages: 31-42
  • Peer Reviewed
• [Journal Article] Efficacy of 23-valent pneumococcal vaccine in preventing pneumonia and improving survival in nursing home residents: double blind (2010)
  • Author(s): Maruyama T, Taguchi O, Niederman MS, Morser J, Kobayashi H, Kobayashi T,D'Alessandro-Gabazza C, Nakayama S, Nishikubo K, Noguchi T, Takei Y, Gabazza EC.
  • Journal Title: randomised and placebocontrolled trial. BMJ Volume: 340 Pages: c1004
  • DOI: DOI:10.1165/rcmb.2011-0158OC
  • Peer Reviewed
• [Presentation] 気道リモデリング制御方法としてのRNAi創薬の試み (2012)
  • Author(s): 小林 哲
  • Organizer: 臨床喘息研究会 第20回学術講演会
  • Place of Presentation: 金沢
  • Year and Date: 2012-10-06
• [Presentation] 呼吸器疾患におけるRNAiを用いた治療の可能性 (2012)
  • Author(s): 小林 哲
  • Organizer: 第85回閉塞性肺疾患研究会
  • Place of Presentation: 東京
  • Year and Date: 2012-07-21
• [Presentation] 気道リモデリングにおけるメカニカルストレスの関与の検討 (2012)
  • Author(s): 小林 哲
  • Organizer: 第84回閉塞性肺疾患研究会
  • Place of Presentation: 東京
  • Year and Date: 2012-01-28
• [Presentation] 気道リモデリングにおけるECM contraction および degradationの検討 (2011)
  • Author(s): 小林 哲
  • Organizer: 第19回学術講演会
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-19