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Curcumin inhibits proliferation, migration and neointimal formation of vascular smooth muscle via activating miR-22
Pharmaceutical Biology ( IF 3.9 ) Pub Date : 2020-01-01 , DOI: 10.1080/13880209.2020.1781904
Minghua Zhang 1, 2 , Yuntian Li 1, 3 , Hui Xie 1 , Jing Chen 4 , Shiming Liu 4
Affiliation  

Context: Curcumin has antitumor, antioxidative, anti-inflammatory, and anti-proliferative properties.Objective: To investigate the role of miR-22 during curcumin-induced changes in vascular smooth muscle cells (VSMC) and neointima formation in balloon-injured rat abdominal aorta.Materials and methods: Sprague-Dawley rats were randomised to the sham-operated (n = 10), operated control (injured, n = 10), and curcumin treatment (n = 10) groups. miR-22 expression was determined by real-time PCR. SP1 was assessed by western blot and real-time PCR. Rat aortic smooth muscle A7r5 cells were used to determine VSMC proliferation and migration, which were measured by the MTS, EdU staining, Transwell, and wound healing assays.Results: miR-22 levels declined following arterial balloon injury in vivo (48% at 3d, p < 0.05) and serum stimulation in vitro (45% at 24 h, p < 0.01). Functional studies revealed that miR-22 negatively regulated the proliferation and migration of VSMCs by directly targeting the SP1 transcription factor in VSMCs. Curcumin increased the expression of miR-22 (81%, p < 0.05) and decreased the protein expression of SP1 in VSMCs (25%, p < 0.05). miR-22 inhibition was found to attenuate the effects of curcumin on VSMC functions. Curcumin increased miR-22 (46%, p < 0.01), decreased the SP1 protein (19%, p < 0.05), and inhibited vascular neointimal area (48%, p < 0.01) in vivo.Discussion: The miR-22/SP1 pathway is involved in the protective role of curcumin during arterial balloon injury, but the mechanisms remain unclear.Conclusion: miR-22 is involved in the inhibitory effects of curcumin on VSMCs' proliferation, migration and neointima hyperplasia after arterial balloon injury in rats. Curcumin could be used to prevent neointimal hyperplasia after angioplasty.

中文翻译:

姜黄素通过激活 miR-22 抑制血管平滑肌的增殖、迁移和新生内膜形成

背景:姜黄素具有抗肿瘤、抗氧化、抗炎和抗增殖特性。目的:研究 miR-22 在姜黄素诱导的血管平滑肌细胞 (VSMC) 变化和球囊损伤大鼠腹部新内膜形成过程中的作用。主动脉。材料和方法:将 Sprague-Dawley 大鼠随机分为假手术组(n = 10)、手术对照组(受伤,n = 10)和姜黄素治疗组(n = 10)。miR-22的表达通过实时PCR确定。SP1 通过蛋白质印迹和实时 PCR 进行评估。大鼠主动脉平滑肌 A7r5 细胞用于测定 VSMC 增殖和迁移,通过 MTS、EdU 染色、Transwell 和伤口愈合试验测量。结果:体内动脉球囊损伤后 miR-22 水平下降(3d 时 48% , p < 0。05) 和体外血清刺激(24 小时时 45%,p < 0.01)。功能研究表明,miR-22通过直接靶向VSMCs中的SP1转录因子,负向调节VSMCs的增殖和迁移。姜黄素增加了 miR-22 的表达(81%,p < 0.05)并降低了 VSMC 中 SP1 的蛋白表达(25%,p < 0.05)。发现 miR-22 抑制减弱姜黄素对 VSMC 功能的影响。姜黄素在体内增加 miR-22(46%,p < 0.01),降低 SP1 蛋白(19%,p < 0.05),并抑制血管新生内膜区域(48%,p < 0.01)。讨论:miR-22/ SP1通路参与姜黄素在动脉球囊损伤过程中的保护作用,但机制尚不清楚。结论:miR-22参与姜黄素对VSMCs增殖的抑制作用,大鼠动脉球囊损伤后的迁移和新内膜增生。姜黄素可用于预防血管成形术后新生内膜增生。
更新日期:2020-01-01
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