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

• Project/Area Number: 23790922
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: Juntendo University
• Principal Investigator: SATO Tadashi 順天堂大学, 医学部, 助教 (10596993)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 慢性閉塞性肺疾患(COPD) / microRNA / miR-146a / inflammation / smoking / SMP30 / マイクロRNA / 喫煙 / SMP30KOマウス / 炎症 / SMP30ノックアウトマウス / マイクロアレイ解析 / SMP30ﾉｯｸｱｳﾄﾏｳｽ

Research Abstract

Cigarette smoking is the most important cause of chronic obstructive pulmonary disease (COPD), but the mechanisms of pathogenesis are incompletely defined. We have previously reported that senescence marker protein-30 knockout (SMP30-KO) mice can be useful for investigating cigarette smoke-induced pulmonary emphysema. Moreover, we have already shown that miR-146a plays a pathogenetic role in the abnormal inflammatory response in COPD.
Vitamin C-controlled SMP30-KO were given miR-146a inhibitor on day 1 and 8 intranasally during exposure to either diluted cigarette smoke or fresh air for 2 weeks. Total cell and lymphocyte numbers were increased in the BALF of both miR-146a inhibitor and smoke exposed mice. PGE2 production and COX-2 expression were also increased significantly higher by exposure both miR-146a inhibitor and cigarette smoke.
In conclusion, miR-146a appears to play a pathogenetic role in the abnormal inflammatory response in a cigarette smoke-exposed murine model of COPD.

Research Products

• [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 Pages: 347-357
  • DOI: 10.1165/rcmb.2013-0121oc
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Differential Roles of JNK, ERK1/2, and p38 Mitogen-Activated Protein Kinases on Endothelial Cell Tissue Repair Functions in Response to Tumor Necrosis Factor-a (2013)
  • Author(s): Kanaji N, Nelson A, Wang X, Sato T, Nakanishi M, Gunji Y, Basma H, Michalski J, Farid M, Rennard SI, Liu X.
  • Journal Title: J Vasc Res Volume: 50 Pages: 145-156
  • DOI: 10.1159/000345525
  • Peer Reviewed
• [Journal Article] Anti-inflammatory effects of budesonide in human lung fibroblasts are independent of histone deacetylase 2 (2013)
  • Author(s): Wang X, Nelson A, Weiler ZM, Patil A, Sato T, Kanaji N, Nakanishi M, Michalski J, Farid M, Basma H, LeVan TD, Miller-Lasson A, Wieslander E, Muller KC, Holz O, Magnussen H, Rabe KF, Liu X, Rennard SI.
  • Journal Title: J Inflamm Res Volume: 6 Pages: 109-119
  • DOI: 10.2147/jir.s43736
  • Peer Reviewed
• [Journal Article] PGE2 Stimulates VEGF Production through the EP2 Receptor in Cultured Human Lung (2012)
  • Author(s): Nakanishi M, Sato T, Li Y, Nelson A, Farid M, Michalski J, Kanaji N, Wang X, Basma H, Patil A, Goraya J, Liu X, Togo S, Toews ML, Holz O, Muller K, Magnussen H, Rennard SI
  • Journal Title: American Journal of Respiratory Cell and Molecular Biology Volume: 46 Pages: 217-223
  • DOI: 10.1165/rcmb.2010-0115oc
  • Peer Reviewed
• [Journal Article] The p38 mitogen-activated protein kinases modulate endothelial cell survival and tissue repair (2012)
  • Author(s): Kanaji N, Nelson A, Allen-Gipson DS, Sato T, Nakanishi M, Wang X, Li Y, Basma H, Michalski J, Farid M, Rennard SI, Liu X
  • Journal Title: Inflamm Res Volume: 61 Pages: 233-11
  • DOI: 10.1007/s00011-011-0405-7
  • Peer Reviewed
• [Journal Article] Attenuation of Inhibitory PGE2 Signaling in Human Lung Fibroblasts is Mediated by PDE4. (2012)
  • Author(s): 佐藤 匡
  • Journal Title: Am J Respir Cell Mol Biol Volume: 47 Pages: 729-737
  • DOI: 10.1165/rcmb.2012-0057oc
  • Peer Reviewed
• [Journal Article] Interleukin-4 induces differentiation of human embryonic stem cells into "fibrogenic" fibroblast-like cells (2011)
  • Author(s): Sato T, Liu X, Basma H, Togo S, Sugiura H, Nelson A, Nakanishi M, Kanaji N, Wang X, Kim M, Li Y, Michalski J, Farid M, Sharp JG, Rennard SI
  • Journal Title: J Allergy Clin Immun Volume: 127 Pages: 1595-1603
  • DOI: 10.1016/j.jaci.2011.01.049
  • Peer Reviewed
• [Journal Article] Inflammatory Cytokines Regulate Endothelial Cell Survival and Tissue Repair Functions via NF-kB Signaling (2011)
  • Author(s): Kanaji N, Sato T, Nelson A, Wang X, Li Y, Kim M, Nakanishi M, Basma H, Michalski J, Farid M, Chandler M, Pease W, Patil A, Rennard SI, Liu X
  • Journal Title: J Inflamm Res Volume: 4 Pages: 127-38
  • DOI: 10.2147/jir.s19461
  • Peer Reviewed
• [Presentation] MicroRNAs associated with smoking-induced pulmonary emphysema in senescence marker protein-30 knockout mice (2014)
  • Author(s): 佐藤匡
  • Organizer: 第52回日本呼吸器学会総会
  • Place of Presentation: 神戸
  • Year and Date: 2014-04-20
• [Presentation] 慢性閉塞性肺疾患(COPD)の発症と病態に関与するmicroRNA-SMP30ノックアウトマウスを用いた解析- (2013)
  • Author(s): 佐藤匡
  • Organizer: 呼吸不全に関する調査研究班平成25年度第2回総会
  • Place of Presentation: 京都
  • Year and Date: 2013-12-20
• [Presentation] MicroRNAs associated with smoking-induced pulmonary emphysema in senescence marker protein-30 knockout mice (2012)
  • Author(s): 佐藤匡
  • Organizer: American Thoracic Society International Conference 2012
  • Place of Presentation: サンフランシスコ
  • Year and Date: 2012-05-22
• [Presentation] MicroRNAs associated with smoking-induced pulmonary emphysema in senescence marker protein-30 knockout mice. (2012)
  • Author(s): 佐藤 匡
  • Organizer: 第52回日本呼吸器学会総会
  • Place of Presentation: 神戸
• [Presentation] MicroRNAs associated with smoking-induced pulmonary emphysema in senescence marker protein-30 knockout mice. (2012)
  • Author(s): 佐藤 匡
  • Organizer: American Thoracic Society International Conference 2012
  • Place of Presentation: San Francisco
• [Presentation] 慢性閉塞性肺疾患 (COPD)の発症と病態に関与するmicroRNA－SMP30ノックアウトマウスを用いた解析－．
  • Author(s): 佐藤 匡
  • Organizer: 呼吸不全に関する調査研究班 平成25年度第2回総会．
  • Place of Presentation: 京都
• [Book] Annual Review呼吸器 (2011)
  • Author(s): 佐藤匡, 他
  • Publisher: 中外医学社
• [Book] 新しい診断と治療のABC(1)慢性閉塞性肺疾患
  • Author(s): 佐藤匡, 他
  • Publisher: 最新医学社