Involvement of Lamin B1 reduction in accelerated cellular senescence during COPD pathogenesis.

• Project/Area Number: 15K09231
• 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: Jikei University School of Medicine
• Principal Investigator: Jun Araya 東京慈恵会医科大学, 医学部, 准教授 (90468679)
• Research Collaborator: Kuwano Kazuyoshi 東京慈恵会医科大学, 医学部, 教授 (40205266) ; Ito Saburo 東京慈恵会医科大学, 医学部, 大学院生 ; Saito Nayuta 東京慈恵会医科大学, 医学部, 大学院生
• Project Period (FY): 2015-04-01 – 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 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 細胞老化 / オートファジー / ｍTOR / Lamin B1 / Deptor / 慢性閉塞性肺疾患 / ラミンB1

Outline of Final Research Achievements

Accelerated cellular senescence has been implicated in chronic obstructive pulmonary disease (COPD) pathogenesis. Downregulation of lamin B1 has been recognized to be a crucial step for development of full senescence. We showed that laminB1 was reduced by cigarette smoke (CS) and lamin B1 reduction was linked to mTOR activation through Deptor downregulation, resulting in accelerated cellular senescence. Aberrant mTOR activation was associated with increase in mitochondrial mass. Lamin B1 protein levels in lung homogenates showed positive correlations with pulmonary function tests. These findings suggest that lamin B1 reduction is involved in the mechanisms for progression of cellular senescence during COPD pathogenesis through aberrant mTOR activation.

Research Products

• [Journal Article] Pirfenidone inhibits myofibroblast differentiation and lung fibrosis development during insufficient mitophagy. (2017)
  • Author(s): Kurita Y, Araya J, Minagawa S, Hara H, Ichikawa A, Saito N, Kadota T, Tsubouchi K, Sato N, Yoshida M, Kobayashi K, Ito S, Fujita Y, Utsumi H, Yanagisawa H, Hashimoto M, Wakui H, Yoshii Y, Ishikawa T, Numata T, Kaneko Y, Asano H, Yamashita M, Odaka M, Morikawa T, Nakayama K, Kuwano K.
  • Journal Title: Respir Res. Volume: 18(1) Issue: 1 Pages: 114-114
  • DOI: 10.1186/s12931-017-0600-3
  • Peer Reviewed / Open Access
• [Journal Article] Azithromycin attenuates myofibroblast differentiation and lung fibrosis development through proteasomal degradation of NOX4. (2017)
  • Author(s): Tsubouchi K, Araya J, Minagawa S, Hara H, Ichikawa A, Saito N, Kadota T, Sato N, Yoshida M, Kurita Y, Kobayashi K, Ito S, Fujita Y, Utsumi H, Yanagisawa H, Hashimoto M, Wakui H, Yoshii Y, Ishikawa T, Numata T, Kaneko Y, Asano H, Yamashita M, Odaka M, Morikawa T, Nakayama K, Nakanishi Y, Kuwano K.
  • Journal Title: Autophagy Volume: 13(8) Issue: 8 Pages: 1420-1434
  • DOI: 10.1080/15548627.2017.1328348
  • Peer Reviewed
• [Presentation] COPD病態におけるLaminB1発現低下 (2017)
  • Author(s): 斎藤那由多
  • Organizer: 日本呼吸器学会総会
• [Presentation] Role of Lamin B1 in COPD pathogenesis (2017)
  • Author(s): 斎藤那由多
  • Organizer: The European Respiratory Society International Congress
  • Int'l Joint Research
• [Presentation] ラミンB1発現低下のCOPD病態における役割 (2016)
  • Author(s): 斉藤那由多
  • Organizer: 日本呼吸器学会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2016-04-08