Senescence marker protein-30 knockout mouse as a novel murine model of senile lung
Senescence marker protein-30 knockout mouse as a novel murine model of senile lung
复制标题
DOI：
10.1111/j.1440-1827.2003.01603.x
复制
发表时间：
2004-03-01
影响因子：
2.2
通讯作者：
Fukuchi, Y
中科院分区：
文献类型：
--
作者：
Mori, T;Ishigami, A;Fukuchi, Y
衰老标记蛋白30（SMP 30）最初被鉴定为一种新的蛋白质，其表达在大鼠肝脏中以雄激素非依赖性的方式随着衰老而降低，并且具有保护细胞免于凋亡的功能。逆转录-聚合酶链反应（RT-PCR）分析表明，在小鼠肺、肝、肾、睾丸和大脑中均发现了SMP 30 mRNA的转录本。我们检查了衰老过程中小鼠肝脏、肾脏和肺中的SMP 30表达，发现每个组织中SMP 30表达的时间分布不同;肝脏中SMP 30 mRNA水平在1-3月龄时达到峰值，此后下降（1月龄时最高，随后迅速下降，此后肾脏中始终较低），肺中在12月龄时达到峰值。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6-12月龄时强烈检测到。进行形态计量学分析以测量平均线性截距和破坏指数，并且发现与SMP 30 Y/+小鼠相比，在1、3和6月龄时SMP 30 Y/-小鼠的外周气腔扩大而没有肺泡破坏。我们的研究结果表明，SMP 30 Y/-小鼠可能是一种新的模型，老年肺和SMP 30 Y/-小鼠的进一步检查可能提供线索，以阐明老年人肺部疾病的发展机制。
Senescence marker protein-30 (SMP30) was originally identified as a novel protein of which expression decreases in an androgen-independent manner with aging in the rat liver and functions to protect cells from apoptosis. By reverse transcription-polymerase chain reaction analysis, SMP30 mRNA transcripts were found in the mouse lung, liver, kidney, testis and cerebrum. We examined SMP30 expression in the mouse liver, kidney and lung during aging and a distinct temporal profile of SMP30 expression was found in each tissue; the SMP30 mRNA level peaked at 1-3 months of age and decreased thereafter in the liver (the highest at 1 month of age followed by a rapid decline and consistently low thereafter in the kidney), and peaked at 12 months of age in the lung. To investigate the 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 6-12 months of age. Morphometric analysis was performed to measure the mean linear intercept and destructive index, and found peripheral airspace enlargement without alveolar destruction in SMP30Y/- mice at 1, 3 and 6 months of age compared with the SMP30Y/+ mice. Our results strongly suggest that SMP30Y/- mice could be a novel model for a senile lung and further examinations of SMP30Y/- mice may offer clues to elucidate the mechanisms of the development of pulmonary diseases in the elderly.