MiR155 modulates vascular calcification by regulating Akt-FOXO3a signalling and apoptosis in vascular smooth muscle cells.
MiR155 modulates vascular calcification by regulating Akt-FOXO3a signalling and apoptosis in vascular smooth muscle cells.
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DOI：
10.1111/jcmm.16107
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发表时间：
2021-01
影响因子：
5.3
通讯作者：
Fan D
中科院分区：
文献类型：
--
作者：
Li Y;Sun W;Saaoud F;Wang Y;Wang Q;Hodge J;Hui Y;Yin S;Lessner SM;Kong X;Fan D
MicroRNA-155(MiR155)是促动脉粥样硬化的基因；然而，它在血管钙化中的作用尚不清楚。在这项研究中，我们旨在研究miR155是否调节血管钙化并了解其潜在的机制。实时定量聚合酶链式反应显示miR155在人颈动脉钙化组织中高表达，并与成骨基因的表达呈正相关。创伤愈合实验和TUNEL染色显示miR155缺失抑制了血管平滑肌细胞(VSMC)的迁移和凋亡。MiR155缺乏可减弱钙化介质对培养的小鼠VSMC和主动脉环的钙化作用，而miR155过表达则促进VSMC的钙化。与野生型小鼠相比，miR155−/−小鼠对维生素D3诱导的血管钙化表现出显著的抵抗力。蛋白质分析显示，miR155缺乏可减轻VSMC和维生素D3处理组小鼠血管内皮细胞中Rictor的还原，增加S473处Akt的磷酸化，加速FOXO3a的磷酸化和降解。抑制Akt磷酸化的PI3K抑制剂增加，而抑制凋亡的PAN-caspase抑制剂减少VSMC钙化；两种抑制剂都减弱了miR155缺乏对VSMC钙化的保护作用。结论：miR155缺陷通过增加Akt的磷酸化和FOXO3a的降解来减轻血管钙化，从而减少钙化介质诱导的VSMC的凋亡。
microRNA‐155 (miR155) is pro‐atherogenic; however, its role in vascular calcification is unknown. In this study, we aim to examine whether miR155 regulates vascular calcification and to understand the underlying mechanism. Quantitative real‐time PCR showed that miR155 is highly expressed in human calcific carotid tissue and positively correlated with the expression of osteogenic genes. Wound‐healing assay and TUNEL staining showed deletion of miR155 inhibited vascular smooth muscle cell (VSMC) migration and apoptosis. miR155 deficiency attenuated calcification of cultured mouse VSMCs and aortic rings induced by calcification medium, whereas miR155 overexpression promoted VSMC calcification. Compared with wild‐type mice, miR155−/− mice showed significant resistance to vitamin D3 induced vascular calcification. Protein analysis showed that miR155 deficiency alleviated the reduction of Rictor, increased phosphorylation of Akt at S473 and accelerated phosphorylation and degradation of FOXO3a in cultured VSMCs and in the aortas of vitamin D3‐treated mice. A PI3K inhibitor that suppresses Akt phosphorylation increased, whereas a pan‐caspase inhibitor that suppresses apoptosis reduced VSMC calcification; and both inhibitors diminished the protective effects of miR155 deficiency on VSMC calcification. In conclusion, miR155 deficiency attenuates vascular calcification by increasing Akt phosphorylation and FOXO3a degradation, and thus reducing VSMC apoptosis induced by calcification medium.
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影响因子：
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作者：
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