MicroRNAs associated with smoking-induced pulmonary emphysema in senescence marker protein-30 knockout mice

2017 Fiscal Year Final Research Report

• Project/Area Number: 26461199
• 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: Juntendo University
• Principal Investigator: Sato Tadashi 順天堂大学, 医学部, 准教授 (10596993)
• Co-Investigator(Kenkyū-buntansha): 瀬山 邦明 順天堂大学, 医学部, 先任准教授 (10226681) ; 高橋 史行 順天堂大学, 医学部, 准教授 (70327823)
• Co-Investigator(Renkei-kenkyūsha): ISHIGAMI Akihito 東京都健康長寿医療センター研究所, 老化制御研究チーム, 研究部長 (50270658)
• Research Collaborator: RENNARD Stephen I. ネブラスカ大学, 医療センター, 教授 ; SUZUKI Yohei 順天堂大学, 医学部, 助教 ; MITSUI Aki 順天堂大学, 医学部, 実験助手
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: microRNA / 慢性閉塞性肺疾患(COPD) / miR-146a / 喫煙 / 炎症 / COX-2 / IL-8

Outline of Final Research Achievements

Cigarette smoking is the most important cause of COPD, but the mechanisms of pathogenesis are incompletely defined. We have reported that a specific microRNA, miR-146a, plays a pathogenetic role in the abnormal inflammatory response in COPD. In the current study, we investigated the role of miR-146a in acute phase of inflammatory response towards cigarette smoking. Interleukin-8 was significantly increased in BEAS-2B cells, normal human bronchial epithelial cells, following 6 days of cigarette smoke extract (CSE) and 2 days of lipopolysaccharide (LPS) compared with non-CSE treatment cells (70.2→118.1 pg/mL, P<0.01). Additionally, LPS-induced miR-146a expression was also increased significantly by pretreatment of CSE (relative expression: 44.0→70.1, P<0.01). Together, LPS-induced inflammatory response was clearly enhanced by CSE pretreatment in human bronchial epithelial cells. Moreover, miR-146a may associate with the acute inflammatory response during the exacerbation of COPD.

Free Research Field

呼吸器内科学