Cigarette smoke-induced lung pathology in SMP30 knockout mice

SMP30 基因敲除小鼠香烟烟雾诱发的肺部病理学

• 批准号: 13470130
• 负责人: FUKUCHI Yoshinosuke
• 金额: $ 5.7万
• 依托单位: JUNTENDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470130/
• 关键词: Emphysema; SMP30; Ageing; Knockout mice; bronchial epithelial cells; apoptosis; smoke exposure; bronchial inflammation

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.

衰老标志蛋白30（SMP 30）是一种新发现的蛋白质，其表达水平随着衰老而降低，并具有保护细胞免于凋亡的功能。通过逆转录-聚合酶链反应（RT-PCR）分析，在小鼠肺、肝脏、肾脏、睾丸和大脑中发现了SMP 30 mRNA转录本。我们研究了C57/BL 6小鼠肺、肾和肝在衰老过程中的SMP 30表达，发现每个组织中SMP 30表达的时间分布不同。在肺中，SMP 30 mRNA水平在出生后逐渐增加，在12月龄时达到峰值，此后下降。为了研究SMP 30在肺中的生理作用，进行野生型（SMP 30 Y/+）小鼠的免疫组织化学研究和SMP 30敲除（SMP 30 Y/-）小鼠的组织病理学检查。抗SMP 30抗体的免疫反应主要在支气管上皮细胞中检测到，并在6至12月龄时强烈检测到。在肺中的Clara细胞、肺泡巨噬细胞和浆细胞中也证实了阳性免疫染色。形态计量学分析测量平均线性截距（MLI）和破坏指数（DI），发现与SMP 30 Y/+小鼠相比，SMP 30 Y/-小鼠在1、3和6月龄时的外周空气腔扩大而没有肺泡破坏。当将3月龄的野生型（SMP 30 Y/+）和SMP 30 Y/-小鼠暴露于1%香烟烟雾（iRi研究香烟）1个月时，与溶剂对照相比，SMP 30 Y/-小鼠的MLI显著增加，但野生型（SMP 30 Y/+）小鼠的MLI未增加。我们的研究结果强烈表明，SMP 30 Y/-小鼠可能是一种新的模型，老年肺，并成为肺气肿模型时，暴露于香烟烟雾。对SMP 30 Y/-小鼠的进一步研究可能为阐明老年人肺部疾病的发生机制提供线索。

项目成果

Mori T, et al.: "Senescence marker protein-30 knockout mouse as a novel murine model of senile lung"Pathology International. 54. 167-173 (2004)

Mori T 等人：“衰老标记蛋白 30 敲除小鼠作为老年肺的新型小鼠模型”国际病理学。

Mori T, et al.: "Senescence marker protein-30 knockout mouse as a novel model of senile lung"Pathology International. 54. 167-173 (2004)

Mori T 等人：“衰老标记蛋白 30 敲除小鼠作为老年肺的新型模型”国际病理学。