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

• 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
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: microRNA / 慢性閉塞性肺疾患(COPD) / miR-146a / 喫煙 / 炎症 / COX-2 / IL-8 / エクソソーム / 気管支洗浄液 / 気道上皮細胞 / タバコ煙抽出液 / COPD増悪 / NF-kB / SMP30ノックアウトマウス

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.

Research Products

• [Journal Article] Hydrogen-rich pure water prevents cigarette smoke-induced pulmonary emphysema in SMP30 knockout mice (2017)
  • Author(s): Suzuki Yohei、Sato Tadashi、Sugimoto Masataka、Baskoro Hario、Karasutani Keiko、Mitsui Aki、Nurwidya Fariz、Arano Naoko、Kodama Yuzo、Hirano Shin-ichi、Ishigami Akihito、Seyama Kuniaki、Takahashi Kazuhisa
  • Journal Title: Biochem Biophys Res Commun. Volume: 492 Issue: 1 Pages: 74-81
  • DOI: 10.1016/j.bbrc.2017.08.035
  • Peer Reviewed
• [Journal Article] Elimination of p19ARF-expressing cells enhances pulmonary function in mice. (2016)
  • Author(s): 1.Hashimoto M., Asai A., Kawagishi H., Mikawa R., Iwashita Y., Kanayama K., Sugimoto K., Sato T., Maruyama M., and Sugimoto M.
  • Journal Title: JCI insight Volume: 1 Issue: 12
  • DOI: 10.1172/jci.insight.87732
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MicroRNAs as Therapeutic Targets in Lung Disease: Prospects and Challenges (2016)
  • Author(s): Sato T, Baskoro H, Rennard SI, Seyama K, Takahashi K.
  • Journal Title: Chronic Obstr Pulm Dis (Miami) Volume: 3 Issue: 1 Pages: 382-388
  • DOI: 10.15326/jcopdf.3.1.2015.0160
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Antioxidant nutrients in plasma of Japanese patients with chronic obstructive pulmonary disease, asthma-COPD overlap syndrome, and bronchial asthma (2016)
  • Author(s): Kodama Y, Kishimoto Y, Muramatsu Y, Tatebe J, Yamamoto Y, Hirota N, Itoigawa Y, Atsuta R, Koike K, Sato T, Aizawa K, Takahashi K, Morita T, Homma S, Seyama K, Ishigami A.
  • Journal Title: Clin Respir J Volume: ー Issue: 6 Pages: 1-10
  • DOI: 10.1111/crj.12436
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prostaglandin E2 switches from a stimulator to an inhibitor of cell migration after epithelial-to-mesenchymal transition. Prostaglandins Other Lipid Mediat (2015)
  • Author(s): 2)Li YJ, Kanaji N, Wang XQ, Sato T, Nakanishi M, Kim M, Michalski J, Nelson AJ, Farid M, Basma H, Patil A, Toews ML, Liu X, Rennard SI.
  • Journal Title: Prostaglandins Other Lipid Mediat Volume: 116-117 Pages: 1-9
  • DOI: 10.1016/j.prostaglandins.2014.10.003
  • Peer Reviewed / Open Access
• [Journal Article] Vitamin C Prevents Cigarette Smoke-Induced Pulmonary Emphysema in Mice and Provides Pulmonary Restoration. (2014)
  • Author(s): Koike K, Ishigami A, Sato Y, Hirai T, Yuan Y, Kobayashi E, Tobino K, Sato T, Sekiya M, Takahashi K, Fukuchi Y, Maruyama N, Seyama K.
  • Journal Title: Am J Respir Cell Mol Biol. Volume: 50 Issue: 2 Pages: 347-357
  • DOI: 10.1165/rcmb.2013-0121oc
  • Peer Reviewed
• [Journal Article] Fibroblasts that resist cigarette smoke-induced senescence acquire pro-fibrotic phenotypes (2014)
  • Author(s): Kanaji N, Basma H, Nelson A, Farid M, Sato T, Nakanishi M, Wang X, Michalski J, Li Y, Gunji Y, Feghali-Bostwick CA, Liu X, Rennard SI
  • Journal Title: Am J Physiol Lung Cell Mol Physiol Volume: 307 Issue: 5 Pages: 364-373
  • DOI: 10.1152/ajplung.00041.2014
  • Peer Reviewed
• [Presentation] COPDモデルマウスを用いたビタミンC治療による肺胞修復メカニズムの遺伝子学的解析 (2017)
  • Author(s): 荒野直子、佐藤匡、烏谷惠子、Hario Baskoro、鈴木洋平、三井亜樹、児玉裕三、近藤嘉高、石神昭人、瀬山邦明、高橋和久
  • Organizer: 第57回日本呼吸器学会学術講演会
• [Presentation] Regional heterogeneity of airway epithelial cells in response to cigarette smoke extract (2017)
  • Author(s): Hario Baskoro, Tadashi Sato, Keiko Karasutani, Yohei Suzuki, Naoko Arano, Moegi Komura, Mitsuaki Sekiya, Yuzo Kodama, Kuniaki Seyama, Kazuhisa Takahashi
  • Organizer: 第57回日本呼吸器学会学術講演会
• [Presentation] COPD増悪症例における再増悪と安定期治療との関連について (2017)
  • Author(s): 小村萌起、荒野直子、佐藤匡、鈴木洋平、吉川仁美、柳下薫寛、佐々木信一、高橋和久
  • Organizer: 第57回日本呼吸器学会学術講演会
• [Presentation] Hydrogen-rich pure water prevents cigarette smoke-induced pulmonary emphysema in SMP30 knockout mice (2017)
  • Author(s): Yohei Suzuki, Tadashi Sato, Masataka Sugimoto, Hario Baskoro, Keiko Karasutani, Aki Mitsui, Yuzo Kodama, Mitsuaki Sekiya, Akihito Ishigami, Kuniaki Seyama, Kazuhisa Takahashi
  • Organizer: American Thoracic Society International Conference 2017
  • Int'l Joint Research
• [Presentation] COPD急性増悪におけるmicroRNA-146aの役割の解明 (2016)
  • Author(s): 烏谷惠子、佐藤匡、Hario Baskoro、鈴木洋平、関谷充晃、児玉裕三、瀬山邦明、高橋和久
  • Organizer: 第56回日本呼吸器学会学術講演会
  • Place of Presentation: 京都
  • Year and Date: 2016-04-08
• [Presentation] MiR-146a plays a pathogenetic role in the abnormal inflammatory lung response of the chronic obstructive pulmonary disease model mice (2015)
  • Author(s): Tadashi Sato, Hario Baskoro, Aki Mitsui, Motoyasu Kato, Yohei Suzuki, Keiko Karasutani, Mitsuaki Sekiya, Yuzo Kodama, Fumiyuki Takahashi, Kuniaki Seyama, Kazuhisa Takahashi
  • Organizer: American Toracic Society International Conference 2015
  • Place of Presentation: Denver (U.S.A.)
  • Year and Date: 2015-05-15 – 2015-05-20
• [Presentation] MiR-146a plays a pathogenetic role in the abnormal inflammatory lung response of the chronic obstructive pulmonary disease model mice (2015)
  • Author(s): Tadashi Sato, Hario Baskoro, Aki Mitsui, Motoyasu Kato, Yohei Suzuki, Keiko Karasutani, Mitsuaki Sekiya, Yuzo Kodama, Fumiyuki Takahashi, Kuniaki Seyama, Kazuhisa Takahashi
  • Organizer: American Thoracic Society International Conference 2015
  • Place of Presentation: Denver (USA)
  • Year and Date: 2015-05-15
  • Int'l Joint Research
• [Presentation] MiR-146a plays a pathogenetic role in the abnormal inflammatory response in the lungs of a murine COPD model (2015)
  • Author(s): Hario Baskoro, Tadashi Sato, Motoyasu Kato, Yohei Suzuki, Keiko Karasutani, Mitsuaki Sekiya, Yuzo Kodama, Fumiyuki Takahashi, Kuniaki Seyama, Kazuhisa Takahashi
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京国際フォーラム（東京）
  • Year and Date: 2015-04-17 – 2015-04-19
• [Presentation] MiR-146a plays a pathogenetic role in the abnormal inflammatory response in the lungs of a murine COPD model (2015)
  • Author(s): Hario Baskoro, Tadashi Sato, Motoyasu Kato, Yohei Suzuki, Keiko Karasutani, Mitsuaki Sekiya, Yuzo Kodama, Fumiyuki Takahashi, Kuniaki Seyama, Kazuhisa Takahashi
  • Organizer: 第55回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2015-04-17
• [Presentation] miR-146a Plays Pathogenic Role in Abnormal Inflammatory Response of a Murine COPD Model (2014)
  • Author(s): Hario Baskoro, Tadashi Sato, Aki Mitsui, Yohei Suzuki, Fumiyuki Takahashi, Motoyasu Kato, Fariz Nurwidya, Kuniaki Seyama, Kazuhisa Takahashi.
  • Organizer: The 19th Congress of the Asian Pacific Society of Respirology: APSR 2014
  • Place of Presentation: Bali (Indonesia)
  • Year and Date: 2014-11-13 – 2014-11-16
• [Book] Chronic Obstructive Pulmonary Disease A Systemic Inflammatory Disease (2017)
  • Author(s): Sato T, Seyama K
  • Total Pages: 352
  • Publisher: Springer
  • ISBN: 9789811008382
• [Book] Chronic Obstructive Pulmonary Disease. A Systemic Inflammatory Disease (2017)
  • Author(s): Sato T, Seyama K
  • Total Pages: 352
  • Publisher: Springer