H3K9me3 参与调节高糖诱导大鼠胸主动脉平滑肌细胞增殖

目的:研究H3K9me3在高糖诱导大鼠胸主动脉平滑肌A7r5细胞增殖中的作用,并初步探讨其可能的作用机制。方法:应用MTT法检测高糖刺激下不同浓度的H3K9甲基转移酶SUV39H1特异性抑制剂Chaetocin(0、10、25、50、75、100 nmol/L)和50nmol/L H3K9甲基转移酶SUV39H1特异性抑制剂Chaetocin在不同时间点(24、48、72 h和5 d)对细胞增殖的影响。应用Western bolt法观察50 nmol/L H3K9甲基转移酶SUV39H1特异性抑制剂Chaetocin在高糖浓度下干预A7r5细胞72 h后,对H3K9me3和p53表达的影响。结果:Chaetocin可显著抑制高糖诱导下A7r5细胞的增殖,且抑制作用呈浓度和时间依赖性。与正常糖相比,Chaetocin可显著下调A7r5细胞在高糖诱导下表达增多的H3K9me3,同时显著上调在高糖诱导下表达减少的p53(P0.05)。结论:高糖可通过H3K9me3下调p53的表达促进大鼠胸主动脉平滑肌A7r5细胞的增殖,H3K9甲基转移酶SUV39H1特异性抑制剂Chaetocin可抑制上述过程,为减少糖尿病大血管并发症提供了治疗的新思路。

H3K9me3 is involved in Proliferation of Rat Thoracic Aortic Smooth Muscle Cells induced by High Glucose*

Objective:To explore the effects of H3K9me3 on rat thoracic aortic smooth muscle A7r5 cell proliferation induced by high glucose, and to study its underlying mechanism.Methods:Under the high glucose condition, MTT assays were applied to observe the effects of different concentrations of H3K9 methyltransferase SUV39H1 specific inhibitor Chaetocin (0, 10, 25, 50, 75, 100 nmol/L) and 50 nmol/L Chaetocin at different time points (24, 48, 72 h, 5 d)on rat thoracic aortic muscle A7r5 cell proliferation, respectively. Western bolt was used to explore the protein expression of H3K9me3 and p53 after 50 nmol/L Chaetocin incubating A7r5 cells for 72 h.Results:Chaetocin can significantly suppressed A7r5 cell proliferation induced by high glucose in a concentration- and time- dependent manner. Compared with normal concentration of glucose, Chaetocin significantly inhibited the up-regulated expression of H3K9me3 and increased the down-regulated expression of p53 induced by high glucose in A7r5 cells (P<0.05).Conclusion:Down-regulated p53 can enhance the proliferation of rat thoracic aortic muscle cell induced by high glucose via H3K9me3, while H3K9 methyltransferase inhibitor Chaetocin can suppressed this process, which provides a new insight for the treatment of diabetic macroangiopathy.