Development of new therapeutic strategies for chronic obstructive diseases using RNA interference

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591128
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Mie University
• Principal Investigator: GABAZZA Esteban 三重大学, 医学(系)研究科(研究院), 教授 (00293770)
• Co-Investigator(Kenkyū-buntansha): KOBAYASHI Tetsu 三重大学, 医学部附属病院, 講師 (20437114)
• Co-Investigator(Renkei-kenkyūsha): MORSER John 三重大学, 医学系研究科, 客員教授 (40571625)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 肺気腫 / 細胞内伝達機構 / NF-kappaB / RNA干渉 / プロテアーゼ / MMP-2 / 煙草 / 炎症性サイトカイン

Outline of Final Research Achievements

In the present research project, we developed a novel metalloproteinase-(MMP-)2 transgenic mouse that showed characteristic findings of chronic obstructive pulmonary disease (COPD) after short-term exposure to inhaled cigarette smoke extracts. Wild type mice usually required exposure to cigarette smoke extracts of more than half-a-year to develop COPD typical findings in the lungs. In addition, this study evaluated the therapeutic usefulness of NF-kappaB siRNA in COPD using our present mouse model. Compared to control, intranasal administration of NF-kappaB siRNA significantly suppressed lung pathological changes, cell inflammation and inflammatory cytokines. The results of this study suggest the potential therapeutic usefulness of siRNA against NF-kappaB signal pathways in COPD.

Free Research Field

免疫学