Effects of Rosiglitazone on the Proliferation of Vascular Smooth Muscle Cell Induced by High Glucose
Effects of Rosiglitazone on the Proliferation of Vascular Smooth Muscle Cell Induced by High Glucose
复制标题
罗格列酮对高糖诱导血管平滑肌细胞增殖的影响
DOI：
10.1007/s10557-008-6127-6
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发表时间：
2008-12-01
影响因子：
3.4
通讯作者：
Liao, Duan-Fang
中科院分区：
文献类型：
--
作者：
Ling, Hong-Yan;Hu, Bi;Liao, Duan-Fang
目的探讨增敏剂罗格列酮对高糖诱导的大鼠血管平滑肌细胞（VSMC）增殖的影响。MTT法和细胞计数法检测VSMC增殖情况。流式细胞仪检测细胞周期。Western blotting检测增殖细胞核抗原（PCNA）和基质金属蛋白酶-2（MMP-2）的蛋白表达。RT-PCR检测MMP-2 mRNA表达，酶谱法检测明胶分解活性。结果促VSMC增殖可显著增加S期VSMCs数量、PCNA和MMP-2表达及MMP-2活性，降低G 0/G1期VSMCs比例。罗格列酮10 μmol/L可明显抑制葡萄糖诱导的VSMC增殖（1.869 ± 0.22vs0.820 ± 0.15，P < 0.01）。同时，罗格列酮抑制PCNA表达，（0.96 ± 0.07vs0.75 ± 0.06，P < 0.05），细胞周期由G 0/G1期进入S期G 0/G1期细胞占69.6 ± 3.96%，S期细胞占25.2 ± 1.73%，S期细胞占10.1 ± 1.42%（P< 0.01）。罗格列酮显著降低MMP-2 mRNA表达（0.98 ± 0.08vs0.71 ± 0.05，P < 0.05），蛋白表达（0.80 ± 0.04vs0.64 ± 0.03，P < 0.05）和MMP-2活性结论罗格列酮可明显抑制高糖诱导的VSMC增殖，其机制可能与抑制高糖诱导的G1→S期转化、PCNA表达和MMP-2合成有关。
AimTo investigate the effects of the sensitizer rosiglitazone on the proliferation of vascular smooth muscle cell (VSMC) induced by high glucose administration.MethodsVSMCs were isolated from rat thoracic aortas and cultured in 10% fetal bovine serum (FBS). VSMC proliferation was evaluated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cell counting. The cell cycle was examined by flow cytometry. The protein expressions of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinases-2 (MMP-2) were evaluated by Western blotting. MMP-2 mRNA expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and gelatinolytic activity was determined by zymography.ResultsPromoted VSMC proliferation significantly increased the number of VSMCs in the S phase, the expressions of PCNA and MMP-2, and MMP-2 activity, as well as decreased the proportion of VSMCs in the G0/G1phase. Rosiglitazone at a concentration of 10 μmol/L markedly inhibited glucose-induced VSMC proliferation (1.869 ± 0.22 vs 0.820 ± 0.15,P< 0.01). Concomitantly, rosiglitazone inhibited PCNA expression (0.96 ± 0.07 vs 0.75 ± 0.06,P< 0.05) and cell cycle progression from G0/G1to S phase (the proportion of VSMCs in the G0/G1and S phase were 69.6 ± 3.96% vs 84.3 ± 1.73% and 25.2 ± 1.73% vs 10.1 ± 1.42% (P< 0.01), respectively). Furthermore, rosiglitazone significantly decreased MMP-2 mRNA expression (0.98 ± 0.08 vs 0.71 ± 0.05,P< 0.05), protein expression (0.80 ± 0.04 vs 0.64 ± 0.03,P< 0.05) and MMP-2 activity (320 ± 25% vs 248 ± 21%,P< 0.05).ConclusionRosiglitazone significantly inhibited VSMC proliferation, at least in part by inhibiting high glucose-induced G1→S phase transition, PCNA expression and MMP-2 synthesis.