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周期性张应变通过 microRNA-187-3p 促进人主动脉平滑肌细胞增殖和迁移,减少其凋亡。

Cyclic tensile strain facilitates proliferation and migration of human aortic smooth muscle cells and reduces their apoptosis via miRNA-187-3p.

机构信息

Department of Ophthalmology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

Department of Vascular Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

出版信息

Bioengineered. 2021 Dec;12(2):11439-11450. doi: 10.1080/21655979.2021.2009321.

Abstract

The cardiovascular is a system that contains extremely complex mechanical factors, in which the circulatory flow of blood has rich mechanical laws. Many studies have revealed that mechanical factors play a very important role in the process of revascularization. Hence, it is essential to investigate the mechanical factors in the process of revascularization in depth. A cyclic tensile strain (CTS) was applied to human aortic smooth muscle cells (HASMCs) at a frequency of 1 Hz and amplitudes of 5%, 10% and 15%, respectively. SmallRNA-seq was used to identify differentially expressed miRNAs (DE-miRNAs) responding to CTS in HASMCs. Starbase database predicted the target genes of DE-miRNAs. Metascape was applied for GO and KEGG pathway enrichment analysis and protein-protein interaction network construction. The proliferation and migration of CTS-treated HASMCs were significantly enhanced, and apoptosis were significantly reduced compared to the control group. SmallRNA-seq results demonstrated that 55, 16 and 16 DE-miRNAs were present in 5%, 10% and 15% CTS-treated HASMCs, respectively. Compared to controls, with miR-26a-2-3p and miR-187-3p being the intersection of these DE-miRNAs. Starbase database identified 189 common target genes for miR-26a-2-3p and miR-187-3p. Common target genes are mainly enriched in the basolateral plasma membrane and endocytosis. Further, experiments exhibited that CTS upregulated miR-187-3p expression, and miR-187-3p enhanced the proliferation and migration of HASMCs and reduced their apoptosis. It is suggested that miR-187-3p may be an important target for CTS participate in the process of cardiovascular disease.[Figure: see text].

摘要

心血管系统是一个包含极其复杂力学因素的系统,其中血液的循环流动具有丰富的力学规律。许多研究表明,力学因素在再血管化过程中起着非常重要的作用。因此,深入研究再血管化过程中的力学因素至关重要。将人主动脉平滑肌细胞(HASMCs)分别施加频率为 1 Hz、幅度为 5%、10%和 15%的循环拉伸应变(CTS)。采用 smallRNA-seq 鉴定 CTS 作用下 HASMCs 中差异表达的 microRNA(DE-miRNA)。Starbase 数据库预测 DE-miRNA 的靶基因。Metascape 用于 GO 和 KEGG 通路富集分析和蛋白质-蛋白质相互作用网络构建。与对照组相比,CTS 处理后的 HASMCs 增殖和迁移明显增强,凋亡明显减少。smallRNA-seq 结果表明,5%、10%和 15% CTS 处理的 HASMCs 中分别存在 55、16 和 16 个 DE-miRNA。与对照组相比,miR-26a-2-3p 和 miR-187-3p 是这些 DE-miRNA 的交集。Starbase 数据库鉴定出 miR-26a-2-3p 和 miR-187-3p 的 189 个共同靶基因。共同靶基因主要富集在基底外侧质膜和内吞作用中。进一步实验表明,CTS 上调了 miR-187-3p 的表达,miR-187-3p 增强了 HASMCs 的增殖和迁移,减少了其凋亡。这表明 miR-187-3p 可能是 CTS 参与心血管疾病过程的一个重要靶标。[图:见正文]。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d42/8810176/cb9262d70f8c/KBIE_A_2009321_UF0001_OC.jpg

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