平滑肌分化标志物SM22蛋白具有调节应力纤维形成和血管平滑肌收缩性的生理功能；在衰老的细胞，SM22表达上调，SM22已被公认是新的细胞衰老标志物。我们前期发现，过表达SM22可阻断平滑肌细胞生长信号转导、上调p21、抑制细胞周期进程。我们假设，SM22蓄积诱发细胞衰老和血管老化。本项目将分别从SM22代谢更新、actin细胞骨架组构和信号途径等方面探讨SM22蓄积与平滑肌细胞衰老的因果关系；考查衰老刺激下，SM22基因表达与泛素化降解之间动态平衡变化和调节机制，及其对细胞衰老应答的影响；SM22蓄积对actin细胞骨架组构的影响及在细胞衰老中的意义；明确SM22蓄积抑制生长应答、激活衰老相关途径SIRT1-p53和p53-p21轴的分子机制、以及对内皮功能的影响；利用SM22敲除小鼠于颈总动脉过表达SM22,体内验证SM22蓄积促血管老化效应；探寻靶向SM22的抗血管老化防治策略。

It is known that transgenlin (namely SM22), as a marker of vascular smooth muscle cell (VSMC) differentiation, plays key role in regulation of stress fibre formation and vascular contraction. The expression of SM22 is controlled by myocardin which is a coactivator of serum response factor (SRF). The recent studies show that expression of SM22 is upregulated in senescence cells, which increases in p21 and results in cell cycle arrest. However, the mechanism of SM22 induction of senescence is unclear. We hypothesized that accumulation of SM22 promoted VSMC senescence, which was associated with vascular hypertrophy and hypertension. The goals of this project are, 1) to find the direct evidences for involvement of SM22 in VSMC senescence and vascular ageing; 2) to investigate the mechanism of SM22 turnover during cell senescence, and relationship between it and senescence response in VSMCs; 3) to elucidate the fashion and significances of cytoskeleton dynamics induced by SM22 excess, which plays roles and signaling during cell senescence; 4) to determine the effects of SM22-mediated actin cytoskeleton reorganization on the activation of p53-p21 pathways. Our findings will provide novel insight for understanding the molecular mechanisms governing vascular aging development as well as predicting the new molecular therapeutic target for vascular hypertrophy and hypertension.