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Challenges to cell specific epigenetics in the lungs

Research Project

Project/Area Number 21590961
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionHokkaido University

Principal Investigator

BETSUYAKU Tomoko  Hokkaido University, 大学院・医学研究科, 准教授 (60333605)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2010: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2009: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsLCM / マウス / 喫煙 / 細気管支上皮 / miRNA
Research Abstract

MicroRNAs (miRNAs) are a family of non-coding RNA molecules that post-transcriptionally regulate gene expression. It has recently been discovered that changes in expression of miRNAs are involved in development, carcinogenesis and inflammation. However, it is largely unknown how aging and smoking are associated with differential expression of miRNAs in the lungs. The main problem with analyzing miRNA expression in the lungs is the degree of cellular heterogeneity. The use of tissue homogenates inevitably results in average expression levels of all cells present in the lungs, thus potentially masking any differences in the expression of individual miRNAs within specific cell types. We therefore focused on the changes in miRNA expression in bronchiolar epithelium in vivo, since bronchiolar epithelium is an important site in the pathophysiology of COPD as well as in cigarette smoke (CS)-induced animal models of the disease. We demonstrated changes in miRNAs in mouse bronchiolar epithelium by age and CS exposure. We also found that the cessation of smoking differently affected the miRNA profiling by age.

Report

(3 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • Research Products

    (40 results)

All 2010 2009

All Journal Article (24 results) (of which Peer Reviewed: 24 results) Presentation (14 results) Book (2 results)

  • [Journal Article] The role of catalase in pulmonary fibrosis2010

    • Author(s)
      Odajima N, Betsuyaku T, Nagai K, Moriyama C, Wang DH, Takigawa T, Ogino K, Nishimura M
    • Journal Title

      Respir Res 11

      Pages: 183-183

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cigarette smoke induces nucleic acid oxidation in lung fibroblasts2010

    • Author(s)
      Deslee G, Adair-Kirk TL, Betsuyaku T, Woods JC, Moore CH, Gierada DS, Conradi SH, Atkinson JJ, Toennies HM, Battaile JT, Kobayashi DK, Patterson GA, Holtzman MJ, Pierce RA
    • Journal Title

      Am J Respir Cell Mol Biol 43(5)

      Pages: 576-584

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] High levels of extracellular matrix metalloproteinase inducer are expressed in lymphangioleiomyomatosis2010

    • Author(s)
      Odajima N, Betsuyaku T, Yoshida T, Hosokawa T, Nishimura M
    • Journal Title

      Hum Pathol 41(7)

      Pages: 935-943

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aging enhances susceptibility to cigarette smoke-induced inflammation through bronchiolar chemokines2010

    • Author(s)
      Moriyama C, Betsuyaku T, Ito Y, Hamamura I, Hata J, Takahashi H, Nasuhara Y, Nishimura M
    • Journal Title

      Am J Respir Cell Mol Biol 42(3)

      Pages: 304-311

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Laminin gamma2 fragments are increased in the circulation of patients with early phase acute lung injury2010

    • Author(s)
      Katayama M, Ishizaka A, Sakamoto M, Fujishima S, Sekiguchi K, Asano K, Betsuyaku T, Kotani T, Ware LB, Matthay MA, Hashimoto S
    • Journal Title

      Intensice Care Med 36(3)

      Pages: 479-486

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The role of catalase in pulmonary fibrosis.2010

    • Author(s)
      Odajima N, Betsuyaku T, Nagai K, Moriyama C, Wang DH, Takigawa T, Ogino K, Nishimura M.
    • Journal Title

      Respir Res

      Volume: 11

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cigarette smoke induces nucleic-acid oxidation in lung fibroblasts.2010

    • Author(s)
      Deslee G, Adair-Kirk TL, Betsuyaku T, Woods JC, Moore CH, Gierada DS, Conradi SH, Atkinson JJ, Toennies HM, Battaile JT, Kobayashi DK, Patterson GA, Holtzman MJ, Pierce RA.
    • Journal Title

      Am J Respir Cell Mol Biol

      Volume: 43 Pages: 576-584

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High levels of extracellular matrix metalloproteinase inducer are expressed in lymphangioleiomyomatosis.2010

    • Author(s)
      Odajima N, Betsuyaku T, Yoshida T, Hosokawa T, Nishimura M.
    • Journal Title

      Hum Pathol

      Volume: 411 Pages: 935-943

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cigarette smoke induces nucleic acid oxidation in lung fibroblasts2010

    • Author(s)
      Deslee G, Adair-Kirk TL, Betsuyaku T, Woods JC, Moore CH, Gierada DS, Conradi SH, Atkinson JJ, Toennies HM, Battaile JT, Kobayashi DK, Patterson GA, Holtzman MJ, Pierce RA
    • Journal Title

      Am J Respir Cell Mol Biol (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High levels of extracellular matrix metalloproteinase inducer are expressed in lymphangioleiomyomatosis2010

    • Author(s)
      Odajima N, Betsuyaku T, Yoshida T, Hosokawa T, Nishimura M
    • Journal Title

      Hum Pathol (in press)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aging enhances susceptibility to cigarette smoke-induced inflammation through bronchiolar chemokines2010

    • Author(s)
      Moriyama C, Betsuyaku T, Ito Y, Hamamura I, Hata J, Takahashi H, Nasuhara Y, Nishimura M
    • Journal Title

      Am J Respir Cell Mol Biol 42

      Pages: 304-311

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Laminin gamma2 fragments are increased in the circulation of patients with early phase acute lung injury2010

    • Author(s)
      Katayama M, Ishizaka A, Sakamoto M, Fujishima S, Sekiguchi K, Asano K, Betsuyaku T, Kotani T, Ware LB, Matthay MA, Hashimoto S
    • Journal Title

      Intensice Care Med 36

      Pages: 479-486

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aging affects lipopolysaccharide-induced upregulation of heme oxygenase-1 in the lungs and alveolar macrophages2009

    • Author(s)
      Ito Y, Betsuyaku T, Moriyama C, Nasuhara Y, Nishimura M
    • Journal Title

      Biogerontology 10(2)

      Pages: 173-180

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Matrix metalloproteinases in blood from patients with LAM2009

    • Author(s)
      Odajima N, Betsuyaku T, Nasuhara Y, Inoue H, Seyama K, Nishimura M
    • Journal Title

      Respir Med 103(1)

      Pages: 124-129

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] A soluble factor (EMMPRIN) in exudates influences knee motion after total arthroplasty2009

    • Author(s)
      Onodera J, Onodera S, Kondo E, Betsuyaku T, Yasuda K
    • Journal Title

      Knee Surg Sports Traumatol Arthrosc 17(3)

      Pages: 298-304

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between improved airflow limitation and changes in airway caliber induced by inhaled anticholinergic agents in COPD2009

    • Author(s)
      Hasegawa M, Makita H, Nasuhara Y, Odajima N, Nagai K, Ito Y, Betsuyaku T, Nishimura M
    • Journal Title

      Thorax 64(4)

      Pages: 332-338

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Curcumin attenuates elastase-and cigarette smoke-induced pulmonary emphysema in mice2009

    • Author(s)
      Suzuki M, Betsuyaku T, Ito Y,Nagai K, Odajima N, MoriyamaC, Nasuhara Y, Nishimura M
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol 296(4)

      Pages: 614-623

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Epilysin (MMP-28) restrains early macrophage recruitment in Pseudomonas aeruginosa pneumonia2009

    • Author(s)
      Manicone AM, Birkland TP, Lin M, Betsuyaku T, van Rooijen N, Lohi J, Keski-Oja J, Wang Y, Skerrett SJ, Parks WC
    • Journal Title

      J Immunol 182(6)

      Pages: 3866-3876

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aging affects lipopolysaccharide-induced upregulation of heme oxygenase-1 in the lungs and alveolar macrophages2009

    • Author(s)
      Ito Y, Betsuyaku T, Moriyama C, Nasuhara Y, Nishimura M
    • Journal Title

      Biogerontology 10

      Pages: 173-180

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Matrix metalloproteinases in blood from patients with LAM2009

    • Author(s)
      Odajima N, Betsuyaku T, Nasuhara Y, Inoue H, Seyama K, Nishimura M
    • Journal Title

      Respir Med 103

      Pages: 124-129

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A soluble factor (EMMPRIN) in exudates influences knee motion after total arthroplasty2009

    • Author(s)
      Onodera J, Onodera S, Kondo E, Betsuyaku T, Yasuda K
    • Journal Title

      Knee Surg Sports Traumatol Arthrosc 17

      Pages: 298-304

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between improved airflow limitation and changes in airway caliber induced by inhaled anticholinergic agents in COPD2009

    • Author(s)
      Hasegawa M, Makita H, Nasuhara Y, Odajima N, Nagai K, Ito Y, Betsuyaku T, Nishimura M
    • Journal Title

      Thorax 64

      Pages: 332-338

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Curcumin attenuates elastase-and cigarette smoke-induced pulmonary emphysema in mice2009

    • Author(s)
      Suzuki M, Betsuyaku T, Ito Y, Nagai K, Odajima N, Moriyama C, Nasuhara Y, Nishimura M
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol 296

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epilysin(MMP-28)restrains early macrophage recruitment in Pseudomonas aeruginosa pneumonia2009

    • Author(s)
      Manicone AM, Birkland TP, Lin M, Betsuyaku T, van Rooijen N, Lohi J, Keski-Oja J, Wang Y, Skerrett SJ, Parks WC
    • Journal Title

      J Immunol 182

      Pages: 3866-3876

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Aging enhances susceptibility to cigarette smoke-induced inflammation2009

    • Author(s)
      別役智子
    • Organizer
      The 9^<th> World Congress on Inflammation Industry Sponsored Symposium 1
    • Place of Presentation
      東京:京王プラザホテル東京
    • Year and Date
      2009-07-07
    • Related Report
      2010 Final Research Report
  • [Presentation] Aging enhances susceptibility to cigarette smoke-induced inflammation2009

    • Author(s)
      Betsuyaku T
    • Organizer
      The 9th World Congress on Inflammation Industry Sponsored Symposium 1
    • Place of Presentation
      東京:京王プラザホテル東京
    • Year and Date
      2009-07-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] Relationship between improved airflow limitation and changes in airway caliber induced by inhaled anticholinergics in chronic obstructive pulmonary disease2009

    • Author(s)
      Hasegawa M, Nasuhara Y, Makita H, Odajima N, Nagai K, Ito Y, Betsuyaku T, Nishimura M
    • Organizer
      第49回日本呼吸器学会
    • Place of Presentation
      東京:東京国際フォーラム
    • Year and Date
      2009-06-14
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Kinetics of various ocidative stress markers in bronchoalveolar lavage fluid (BALF) in lipopolysaccaride (LPS) induced lung injury2009

    • Author(s)
      Yoshida T, Betsuyaku T, Nagai K, Ito Y, Nasuhara Y, Nishimura M
    • Organizer
      第49回日本呼吸器学会
    • Place of Presentation
      東京:東京国際フォーラム
    • Year and Date
      2009-06-13
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Catalase expression in pulmonary macrophages of smokers and chronic obstructive pulmonary disease (COPD) patients2009

    • Author(s)
      Inomata T, Betsuyaku T, Ito Y, Nasuhara Y, Nishimura M
    • Organizer
      第49回日本呼吸器学会
    • Place of Presentation
      東京:東京国際フォーラム
    • Year and Date
      2009-06-13
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 酸化ストレスによる肺病変としての気腫化と線維化2009

    • Author(s)
      別役智子
    • Organizer
      第49回日本呼吸器学会
    • Place of Presentation
      東京:東京国際フォーラム
    • Year and Date
      2009-06-13
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] アレルギー性気道炎症モデルにおける気道被覆液中のグルタチオン化蛋白の検討2009

    • Author(s)
      長井桂,別役智子,南須原康行,近藤宇史,西村正治
    • Organizer
      第49回日本呼吸器学会
    • Place of Presentation
      東京:東京国際フォーラム
    • Year and Date
      2009-06-13
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] 高齢マウス単回喫煙曝露モデルにおける細気管支上皮細胞でのnuclear factor κB(NF-κB)の活性化とケモカイン発現亢進2009

    • Author(s)
      守山千夏,別役智子,伊藤洋子,西村正治
    • Organizer
      第49回日本呼吸器学会
    • Place of Presentation
      東京:東京国際フォーラム
    • Year and Date
      2009-06-12
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Alveolar-specific gene expression profiling in emphysematous lungs2009

    • Author(s)
      Hersh CP, Betsuyaku T, Patel N, Marchetti N, Klanderman BJ, Criner G, Choi A
    • Organizer
      The 105^<th> American Thoracic Society International Conference
    • Place of Presentation
      The San Diego Convention Center, San Diego, CA, United States
    • Year and Date
      2009-05-17
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Catalase expression in pulmonary macrophages of smokers and chronic obstructive pulmonary disease (COPD) patients2009

    • Author(s)
      Inomata T, Betsuyaku T, Ito Y, Nasuhara Y, Nishimura M
    • Organizer
      The 105^<th> American Thoracic Society International Conference
    • Place of Presentation
      The San Diego Convention Center, San Diego, CA, United States
    • Year and Date
      2009-05-17
    • Related Report
      2010 Final Research Report
  • [Presentation] Protein S-glutathionylation in the Epithelial Lining Fluid during Allergic Airway Inflammation2009

    • Author(s)
      Nagai K, Betsuyaku T,Nasuhara Y, Kondo T, Nishimura M
    • Organizer
      The 105^<th> American Thoracic Society International Conference
    • Place of Presentation
      The San Diego Convention Center, San Diego, CA, United States
    • Year and Date
      2009-05-17
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Duration of cigarette smoke (CS) exposure affects the resolution of lung inflammation after cessation in mice2009

    • Author(s)
      Odajima N, Betsuyaku T, Inomata T, Yoshida T, Moriyama C, Suzuki K, Nagai K, Nasuhara Y, Nishimura M
    • Organizer
      The 105^<th> American Thoracic Society International Conference
    • Place of Presentation
      The San Diego Convention Center, San Diego, CA, United States
    • Year and Date
      2009-05-17
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Kinetics of various oxidative stress markers in BAL fluid in lipopolysaccaride (LPS)-induced lung injury2009

    • Author(s)
      Yoshida T, Betsuyaku T, Nagai K, Ito Y, Nasuhara Y, Nishimura M
    • Organizer
      The 105^<th> American Thoracic Society International Conference
    • Place of Presentation
      The San Diego Convention Center, San Diego, CA, United States
    • Year and Date
      2009-05-17
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Catalase expression in pulmonary macrophages of smokers and chronic obstructive pulmonary disease(COPD)patients2009

    • Author(s)
      Inomata T, Betsuyaku T, Ito Y, Nasuhara Y, Nishimura M
    • Organizer
      The 105^<th> American Thoracic Society International Conference
    • Place of Presentation
      The San Diego Convention Center, San Diego, CA, United States
    • Year and Date
      2009-05-17
    • Related Report
      2009 Annual Research Report
  • [Book] 実験医学増刊 病態解明に迫るI(活性酸素シグナルと酸化ストレス 癌,神経変性疾患,循環・代謝異常にかかわるレドックス制御機構と最新の技術開発)2009

    • Author(s)
      別役智子
    • Publisher
      羊土社
    • Related Report
      2010 Final Research Report
  • [Book] 実験医学増刊 病態解明に迫るI.活性酸素シグナルと酸化ストレス 癌,神経変性疾患,循環・代謝異常にかかわるレドックス制御機構と最新の技術開発2009

    • Author(s)
      別役智子
    • Total Pages
      243
    • Publisher
      羊土社
    • Related Report
      2009 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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