Regulatory mechanisms for senescence marker protein 30 expression

衰老标记蛋白30（SMP 30）被鉴定为在衰老大鼠肝脏中显示显著降低的标记蛋白。调控SMP 30表达的分子机制尚不清楚。阐明这一调控机制对于制定针对与年龄相关的身体素质下降和年龄相关疾病的对策至关重要。衰老是一个高度调节的过程，具有进化保守的信号转导机制，其中胰岛素-胰岛素样生长因子信号转导（IIS）是主要重要的。在本研究中，我发现SMP 30在人HepG 2细胞中的表达受到IIS的调控。对人SMP 30基因的详细分析表明，SMP 30受Forkhead box转录因子O类（FoxO）的调控，FoxO是蠕虫长寿基因daf-16的直系同源物。然而，直接证明FoxO参与几乎是不可行的，因为在HepG 2中SMP 30表达水平极低，可能反映了FoxO调节的辅因子的缺乏。

Senescence marker protein 30 (SMP30) was identified as a marker protein which shows substantial decrease in ageing rat liver. The molecular mechanisms regulating SMP30 expression is unclear. Elucidation of this regulatory mechanisms is crucial for development of countermeasures against age-related decline of physical fitness and age-associated diseases. Ageing is a highly regulated process with evolutionally conserved signal transduction mechanisms, among which insulin-insulin like growth factor signaling (IIS) is predominantly important. In this study, I found that SMP30 expression in human HepG2 cells was regulated by IIS. Detailed analysis of human SMP30 gene indicated that SMP30 is regulated by Forkhead box transcription factor class O (FoxO), an ortholog of worm longevity gene daf-16. However, direct demonstration of FoxO involvement was hardly feasible because of the extremely low level of SMP30 expression in HepG2, probably reflecting lack of cofactor(s) for FoxO regulation.