Cigarette smoke-induced lung pathology in SMP30 knockout mice

Research Project

Project/Area Number	13470130
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Respiratory organ internal medicine
Research Institution	JUNTENDO UNIVERSITY
Principal Investigator	FUKUCHI Yoshinosuke JUNTENDO UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (80010156)
Co-Investigator(Kenkyū-buntansha)	TAKAHASHI Kazuhisa UNTENDO UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 助教授 (80245711) SEYAMA Kuniaki UNTENDO UNIVERSITY, SCHOOL OF MEDICINE, LECTURER, 医学部, 講師 (10226681)
Project Period (FY)	2001 – 2002
Project Status	Completed (Fiscal Year 2002)
Budget Amount *help	¥8,900,000 (Direct Cost: ¥8,900,000) Fiscal Year 2002: ¥4,800,000 (Direct Cost: ¥4,800,000) Fiscal Year 2001: ¥4,100,000 (Direct Cost: ¥4,100,000)
Keywords	Emphysema / SMP30 / Ageing / Knockout mice / bronchial epithelial cells / apoptosis / smoke exposure / bronchial inflammation
Research Abstract	Senescence marker protein-30 (SMP3O) was originally identified as a novel protein of which expression decreases androgen-independent manner with aging in the rat liver and functions to protect cells from apoptosis. By reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, SMP30 mRNA transcripts were found in the mouse lung, liver, kidney, testis and cerebrum. We examined SMP30 expression in the C57/BL6 mouse lung, kidney, and liver during aging and a distinct temporal profile of SMP30 expression was found in each tissues. In the lungs, SMP30 mRNA level gradually increased after birth, peaked at 12 month old, and decreased thereafter. To investigate physiological role of SMP30 in the lung, immunohistochemical studies of wild-type (SMP30Y/+) mice and histopathological examinations of SMP30 knockout (SMP30Y/-) mice were performed. Immunoreactivity against anti-SMP30 antibody was mainly detected in bronchial epithelial cells and strongly detected at 6 to 12 months old. Positive immunostaining was also demonstrated in Clara cells, alveolar macrophages, and plasma cells in the lung. The morphometric analysis was performed to measure mean linear intercept (MLI) and destructive index (DI) and found peripheral airspace enlargement without alveolar destruction in SMP30Y/-mice at 1, 3 and 6 months old compared with that in SMP30Y/+ mice. When wild-type (SMP30Y/+) and SMP30Y/-mice at 3 months of age were exposed to 1% cigarette smoke (iRi research cigarette) for 1 month, MLI significantly increased as compared with vehicle control in SMP30Y/-mice, but not in wild-type (SMP30Y/+) mice. Our results strongly suggest that SMP30Y/-mouse could be a novel model for a senile lung and become a model for emphysema when exposed to cigarette smoke. Further examinations of SMP30Y/-mice may offer clues to elucidate the mechanisms of the development of pulmonary diseases in the elderly.