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

2017 Fiscal Year Final Research Report

• 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
• Keywords: 細胞老化 / オートファジー / ｍTOR / Lamin B1 / Deptor

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.

Free Research Field

医歯薬学・内科系臨床医学・呼吸器内科学