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

2013 Fiscal Year Final Research Report

• 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
• Keywords: 慢性閉塞性肺疾患(COPD) / microRNA / miR-146a / inflammation / smoking / SMP30

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] Prevents Cigarette Smoke-Induced Pulmonary Emphysema in Mice and Provides Pulmonary Restoration (2014)
  • Author(s): Michalski J, Kanaji N, Liu X, Nogel S, Wang X, Basma H, Nakanishi M, Sato T, Gunji Y, Farid M, Nelson A, Muller KC, Holz O, Magnussen H, Rabe KF, Toews ML
  • Journal Title: Am J Respir Cell Mol Biol Volume: 50 Pages: 347-57
  • DOI: 10.1165/rcmb.2013-0121OC
  • Peer Reviewed
• [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: 347-57
  • DOI: 10.1165/rcmb.2013-0121OC
  • Peer Reviewed
• [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: 145-56
  • 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: 109-19
  • DOI: 10.2147/JIR.S43736
  • Peer Reviewed
• [Journal Article] Prostaglandin E2 Stimulates the Production of Vasculaar Endothelial Growth Factor through the E-Prostanoid-2 Receptor in Cultured Human Lung Fibroblasts (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: Am J Respir Cell Mol Biol Volume: 46 Pages: 217-23
  • 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] 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
• [Book] Annual Review呼吸器 (2011)
  • Author(s): 佐藤匡, 他
  • Total Pages: 7-13
  • 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
  • Total Pages: 56-64
  • Publisher: 最新医学社