Cardiovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Cardiovascular Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
Life Sci. 2021 Mar 15;269:118817. doi: 10.1016/j.lfs.2020.118817. Epub 2020 Dec 1.
This study aimed to elucidate the role of microRNAs (miRNAs) during myocardial infarction (MI) development in vivo and in vitro.
Differentially expressed miRNAs between heart tissue from the MI mouse model and the control mouse were identified via microarray. Quantitative PCR (qPCR) and western blotting (WB) were performed to examine the expression levels of miRNAs and proteins, respectively. EdU-staining and colony formation assay were performed to assess cell viability and growth. Annexin V- and PI-staining-based flow cytometry was used to assess cell apoptosis. An MI mouse model was also established to study the function of miR-1278 in vivo.
The levels of miR-1278 were reduced in the infarct regions of heart tissues of the MI mouse model and in HO-treated newborn murine ventricular cardiomyocytes (NMVCs) compared to those in the heart tissues of healthy mice and non-treated NMVCs. HO treatment suppressed the proliferation of NMVCs, while miR-1278 upregulation improved it. Moreover, we found that miR-1278 inhibited the upregulation of IL-22 and CXCL14 expression in HO-treated NMVCs by directly binding with the 3'-UTRs of both IL-22 and CXCL14. Furthermore, restoration of IL-22 and CXCL14 in HO-treated NMVCs promoted miR-1278-induced inflammation and apoptosis. Administration of agomiR-1278 to the MI mouse model significantly improved cardiac activity.
Collectively, our findings illustrate that the expression of miR-1278 is low in HO-treated NMVCs and post-MI cardiac tissues, and the overexpression of miR-1278 in these protects against cell death by modulating IL-22 and CXCL14 expression.
本研究旨在阐明 microRNAs（miRNAs）在体内和体外心肌梗死（MI）发展过程中的作用。
通过微阵列鉴定 MI 小鼠模型和对照小鼠心脏组织中差异表达的 miRNAs。通过定量 PCR（qPCR）和蛋白质印迹（WB）分别检测 miRNA 和蛋白质的表达水平。EdU 染色和集落形成实验评估细胞活力和生长。Annexin V 和 PI 染色基于流式细胞术评估细胞凋亡。还建立了 MI 小鼠模型以研究 miR-1278 在体内的功能。
与健康小鼠和未处理的 NMVCs 的心脏组织相比，MI 小鼠模型和 HO 处理的新生鼠心室心肌细胞（NMVCs）的梗死区中 miR-1278 的水平降低。HO 处理抑制 NMVCs 的增殖，而 miR-1278 的上调改善了增殖。此外，我们发现 miR-1278 通过直接结合 IL-22 和 CXCL14 的 3'-UTRs 抑制 HO 处理的 NMVCs 中 IL-22 和 CXCL14 表达的上调。此外，在 HO 处理的 NMVCs 中恢复 IL-22 和 CXCL14 促进了 miR-1278 诱导的炎症和细胞凋亡。向 MI 小鼠模型中给予 agomiR-1278 可显著改善心脏活动。
总之，我们的研究结果表明，HO 处理的 NMVCs 和 MI 后心脏组织中 miR-1278 的表达水平较低，miR-1278 在这些组织中的过表达通过调节 IL-22 和 CXCL14 的表达来防止细胞死亡。
