m6A Modification Mediates Endothelial Cell Responses to Oxidative Stress in Vascular Aging Induced by Low Fluid Shear Stress.
m6A Modification Mediates Endothelial Cell Responses to Oxidative Stress in Vascular Aging Induced by Low Fluid Shear Stress.
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DOI：
10.1155/2023/8134027
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发表时间：
2023
影响因子：
--
通讯作者：
Liu, Guang
中科院分区：
文献类型：
--
作者：
Xu, Zhijue;Qiu, Peng;Jiang, Yihong;Hu, Jiateng;Wu, Zhaoyu;Lei, Jiahao;Pu, Hongji;Huang, Qun;Wang, Xin;Li, Bo;Ye, Kaichuang;Lu, Xinwu;Liu, Guang
n6 -甲基腺苷（m6A）是最普遍、最丰富的内部转录修饰之一，在多种细胞和生理过程中起着重要作用。低流体剪切应力（FSS）是许多心血管疾病的关键病理因素，它直接作用于血管壁内皮细胞。到目前为止，低FSS时血管内皮细胞中m6A修饰的改变和功能尚不清楚。在此，我们对不同FSS下的HUVECs进行了转录组范围的m6A修饰分析。我们发现m6A修饰在FSS的作用下比mRNA表达更早、更敏感。低FSS增加了CDS区域的m6A修饰，降低了3 ' UTR区域的m6A修饰，并调节了RBM15和EIF3A等m6A调控因子的mRNA表达和m6A修饰。低FSS下高甲基化和低甲基化基因丰富的功能注释表明，m6A修饰聚集在mTOR、PI3K-AKT、胰岛素和ERRB的衰老相关信号通路中，以及氧化应激相关转录因子中，如HIF1A、NFAT5和NFE2L2。我们的研究提供了低FSS下血管内皮细胞m6A修饰的初步观点，揭示了低FSS驱动的m6A修饰介导了细胞对氧化应激和细胞衰老的反应，这表明m6A修饰可能是病理性低FSS下抑制血管衰老的潜在靶点。
N6-methyladenosine (m6A) is one of the most prevalent, abundant, and internal transcriptional modification and plays essential roles in diverse cellular and physiological processes. Low fluid shear stress (FSS) is a key pathological factor for many cardiovascular diseases, which directly forces on the endothelial cells of vessel walls. So far, the alterations and functions of m6A modifications in vascular endothelial cells at the low FSS are still unknown. Herein, we performed the transcriptome-wide m6A modification profiling of HUVECs at different FSS. We found that the m6A modifications were altered earlier and more sensitive than mRNA expressions in response to FSS. The low FSS increased the m6A modifications at CDS region but decreased the m6A modifications at 3′ UTR region and regulated both the mRNA expressions and m6A modifications of the m6A regulators, such as the RBM15 and EIF3A. Functional annotations enriched by the hypermethylated and hypomethylated genes at low FSS revealed that the m6A modifications were clustered in the aging-related signaling pathways of mTOR, PI3K-AKT, insulin, and ERRB and in the oxidative stress-related transcriptional factors, such as HIF1A, NFAT5, and NFE2L2. Our study provided a pilot view of m6A modifications in vascular endothelial cells at low FSS and revealed that the m6A modifications driven by low FSS mediated the cellular responses to oxidative stress and cell aging, which suggested that the m6A modifications could be the potential targets for inhibiting vascular aging at pathological low FSS.
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影响因子：
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作者：
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发表时间：
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影响因子：
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作者：
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