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血管平滑肌细胞增殖是心血管疾病重要的病理生理机制.geminin能够通过调控DNA复制和细胞周期进程在癌细胞的增殖中发挥重要的作用.因此,本研究假设geminin调控了血管平滑肌细胞的增殖.研究结果显示,在静止的血管平滑肌细胞中(约90%细胞处于G1期,10%细胞处于S,G2/M期)geminin低表达,随着更多的细胞进入S,G2/M期,geminin表达水平逐渐升高,而当细胞退出S,G2/M期,geminin表达水平逐渐下降.心血管病理因子血管紧张素Ⅱ和去甲肾上腺素也能刺激血管平滑肌细胞高表达geminin.然而,进一步在血管平滑肌细胞中敲低和过表达geminin后,敲低组和过表达组展示出与各自对照组相似的DNA含量、细胞核形态、细胞周期比例及细胞增殖能力.这一研究结果显示,geminin对血管平滑肌细胞的增殖并不是必需的,这与既往在癌细胞系中的研究结果是不同的,geminin在正常细胞和癌细胞系的这种功能差异提示其可作为一个肿瘤治疗的靶点.
Vascular smooth muscle cell proliferation is an important pathophysiological mechanism of cardiovascular disease.geminin can play an important role in cancer cell proliferation by regulating DNA replication and cell cycle progression.Therefore, we hypothesized that geminin regulates the proliferation of vascular smooth muscle cells The results showed that in stationary vascular smooth muscle cells (about 90% of cells in G1 phase, 10% of cells in S, G2 / M phase) geminin low expression, as more cells into the S, G2 / M phase, geminin expression The level of geminin gradually decreased when the cells exited S, G2 / M phase.Correndothelial angiotensin II and norepinephrine also stimulated the high expression of geminin in vascular smooth muscle cells.However, After knockdown and overexpression of geminin in smooth muscle cells, knockdown and overexpression groups showed similar DNA content, nuclear morphology, cell cycle ratio and cell proliferation ability as compared with their respective control groups.The results of this study show that geminin inhibits vascular smooth muscle The proliferation of cells is not necessary, which is different from the previous findings in cancer cell lines. This function of geminin in normal cells and cancer cell lines The difference suggests that it can be used as a target for cancer treatment.