Geminin蛋白在VSMCs增殖中发挥了重要的调控作用。我们通过沉默Geminin发现可以通过促进VSMCs增殖周期的G0/G1期向S期的转化从而使其增殖速率明显增加。该蛋白在胞核内经泛素-蛋白酶体通路降解，受到泛素化分子调控；而具有UBL结构域及包含E3连接酶的RING结构域的UHRF1蛋白在VSMCs增殖的G1期末和G2/M期大量表达于胞核中，因此我们推UHRF1蛋白可能参与Geminin泛素化调控作用，影响分裂期染色质分离，从而对VSMCs增殖进程发挥重要作用。通过血清培养VSMCs，运用CO-IP、FRET等分析两蛋白间关系，质谱分析及泛素荧光探针检测两蛋白作用方式是否与泛素化降解相关，运用FCM及显微染色体分离技术研究VSMCs染色质分离及增殖周期进程。本课题旨在研究VSMCs增殖及分子调控机制，为探讨其自身调控机制提供一条新思路，从而为增生性血管疾病和PCI术后血管再狭窄的防治提供理论依据。

Geminin plays an important role in regulating VSMCs proliferation.We found that Geminin interference facilitate VSMCs proliferation by promoting the transition the G0/G1 to S phase and it is degradated by ubiquitin - proteasome pathway which is regulated by the ubiquitin molecule in the nucleus. In addition,UHRF1 protein with both UBL domain and RING domain that has E3-ligase is abundantly expressed in the nucleus in the VSMCs proliferation late G1 and G2/M phase. Therefore, we speculate UHRF1 protein may be involved in the ubiquitination-like regulation of Geminin protein,thus it can regulate chromatin segregation in mitotic and play an important regulatory role in VSMCs proliferation cycle. Through FBS stimulates VSMCs proliferation, the relationship between the two proteins was analysised by CO-IP and FRET; whether the mode of action of the two protein were related to the ubiquitination degradation was detected by Mass Spectrometry and Ubiquitin fluorescent probes; chromatin segregation and proliferation process of VSMCs were studied by FCM and microscopic chromatin separation technology. This subject is to study the molecular regulation mechanism in the VSMCs proliferation. It will provide a new mentality for studying the feedback control mechanism in VSMCs proliferation and a new method for treating vascular proliferative diseases and preventing restenosis after angioplasty.