Regulatory mechanisms for senescence marker protein 30 expression

衰老标志蛋白30 （Senescence marker protein 30, SMP30）是衰老大鼠肝脏中显著减少的标志蛋白。调控SMP30表达的分子机制尚不清楚。阐明这种调节机制对于制定对抗与年龄有关的身体素质下降和与年龄有关的疾病的对策至关重要。衰老是一个高度调控的过程，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传导（IIS）最为重要。在本研究中，我发现SMP30在人HepG2细胞中的表达受到IIS的调控。对人类SMP30基因的详细分析表明，SMP30基因受叉头盒转录因子O类（FoxO）调控，FoxO是蠕虫长寿基因daf-16的同源基因。然而，由于SMP30在HepG2中的表达水平极低，直接证明FoxO参与几乎是不可能的，这可能反映了缺乏FoxO调控的辅助因子。

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.