MicroRNA-133 Controls Vascular Smooth Muscle Cell Phenotypic Switch In Vitro and Vascular Remodeling In Vivo
MicroRNA-133 Controls Vascular Smooth Muscle Cell Phenotypic Switch In Vitro and Vascular Remodeling In Vivo
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DOI：
10.1161/circresaha.111.240150
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发表时间：
2011-09-30
影响因子：
20.1
通讯作者：
Indolfi, Ciro
中科院分区：
文献类型：
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作者：
Torella, Daniele;Iaconetti, Claudio;Indolfi, Ciro
理由：MicroRNA (miR)-1和-133在骨骼肌和心肌的生物学和病理生理中起着至关重要的作用。然而，它们在血管细胞生理和疾病中的表达和调控目前尚不清楚。目的：本研究的目的是评估miR-1和miR-133在体外和体内血管平滑肌细胞（VSMC）表型转换中的作用，如果有的话。方法和结果：我们在这里证明，miR-133在体外和体内血管平滑肌细胞（VSMCs）中稳定表达，而miR-1在血管中的水平可以忽略不计。在体外和体内，miR-133对VSMC表型转换具有有效的抑制作用，而miR-1本身没有任何相关作用。miR-133的表达受细胞外信号调节激酶1/2激活的调控，并与VSMC生长呈负相关。事实上，当VSMCs在体外和体内血管损伤后开始增殖时，miR-133会减少，而当VSMCs在体外和体内被诱导恢复静止时，miR-133会增加。miR-133功能丧失和功能获得实验表明，miR-133在VSMC生长中起机制作用。因此，adeno-miR-133减少而anti-miR-133加剧体外和体内VSMC的增殖和迁移。miR-133在体外和体内特异性抑制转录因子Sp-1的表达，通过抑制Sp-1调控平滑肌基因的表达。结论：我们的数据表明，miR-133是体外和体内血管平滑肌细胞表型转换的关键调节因子，提示其在血管疾病的潜在治疗应用。（Circ Res. 2011;109:880-893.）
Rationale: MicroRNA (miR)-1 and -133 play a crucial role in skeletal and cardiac muscle biology and pathophysiology. However, their expression and regulation in vascular cell physiology and disease is currently unknown.Objective: The aim of the present study was to evaluate the role, if any, of miR-1 and miR-133 in vascular smooth muscle cell (VSMC) phenotypic switch in vitro and in vivo.Methods and Results: We demonstrate here that miR-133 is robustly expressed in vascular smooth muscle cells (VSMCs) in vitro and in vivo, whereas miR-1 vascular levels are negligible. miR-133 has a potent inhibitory role on VSMC phenotypic switch in vitro and in vivo, whereas miR-1 does not have any relevant effect per se. miR-133 expression is regulated by extracellular signal-regulated kinase 1/2 activation and is inversely correlated with VSMC growth. Indeed, miR-133 decreases when VSMCs are primed to proliferate in vitro and following vascular injury in vivo, whereas it increases when VSMCs are coaxed back to quiescence in vitro and in vivo. miR-133 loss-and gain-of-function experiments show that miR-133 plays a mechanistic role in VSMC growth. Accordingly, adeno-miR-133 reduces but anti-miR-133 exacerbates VSMC proliferation and migration in vitro and in vivo. miR-133 specifically suppresses the transcription factor Sp-1 expression in vitro and in vivo and through Sp-1 repression regulates smooth muscle gene expression.Conclusions: Our data show that miR-133 is a key regulator of vascular smooth muscle cell phenotypic switch in vitro and in vivo, suggesting its potential therapeutic application for vascular diseases. (Circ Res. 2011;109:880-893.)