Department of Cardiovascular Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, PR China.
Department of Cardiovascular Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, PR China.
J Formos Med Assoc. 2021 Jul;120(7):1512-1519. doi: 10.1016/j.jfma.2020.11.004. Epub 2020 Nov 25.
BACKGROUND/PURPOSE: miR-23a is a pro-hypertrophic miRNA that inhibits M2 macrophage polarization. A previous study demonstrated that lncRNA NRON alleviated atrial fibrosis through suppression of M1 macrophages activated by atrial myocytes. This study aimed to determine whether NRON promotes M2 macrophage polarization and alleviates atrial fibrosis through suppressing exosomal miR-23a derived from atrial myocytes.
Mouse atrial myocytes were transfected with the NRON overexpression vector or empty vector, followed by Ang II treatment. Exosomes were isolated from the treated atrial myocytes and then co-cultured with RAW264.7 macrophages. The culture medium from RAW264.7 macrophages treated as described above was added to mouse atrial fibroblasts for incubation.
We found that exosomes derived from Ang II-treated atrial myocytes inhibited M2 macrophage polarization by transferring miR-23a. NFATc3 could directly bind to the miR-23a promoter. Overexpression of NRON inhibited the expression of miR-23a by inhibiting NFATc3 nuclear transport in Ang II-treated atrial myocytes, resulting in a decrease in the level of miR-23a in atrial myocyte-derived exosomes. Meanwhile, exosomes derived from NRON-overexpressing atrial myocytes promoted M2 macrophage polarization and inhibited expression of fibrosis markers in atrial fibroblasts.
NRON promotes M2 macrophage polarization and alleviates atrial fibrosis through suppressing exosomal miR-23a derived from atrial myocytes.
背景/目的：miR-23a 是一种促肥大的 miRNA，可抑制 M2 巨噬细胞极化。先前的研究表明，lncRNA NRON 通过抑制心房肌细胞激活的 M1 巨噬细胞来减轻心房纤维化。本研究旨在确定 NRON 是否通过抑制来自心房肌细胞的细胞外体 miR-23a 来促进 M2 巨噬细胞极化并减轻心房纤维化。
用 NRON 过表达载体或空载体转染小鼠心房肌细胞，然后用 Ang II 处理。从处理过的心房肌细胞中分离出外泌体，然后与 RAW264.7 巨噬细胞共培养。将如上所述处理的 RAW264.7 巨噬细胞的培养基加入到小鼠心房成纤维细胞中进行孵育。
我们发现，来自 Ang II 处理的心房肌细胞的外泌体通过转移 miR-23a 抑制 M2 巨噬细胞极化。NFATc3 可以直接结合 miR-23a 启动子。NRON 的过表达通过抑制 Ang II 处理的心房肌细胞中 NFATc3 的核转运来抑制 miR-23a 的表达，导致心房肌细胞来源的外泌体中 miR-23a 水平降低。同时，NRON 过表达的心房肌细胞来源的外泌体促进 M2 巨噬细胞极化并抑制心房成纤维细胞中纤维化标志物的表达。
NRON 通过抑制来自心房肌细胞的细胞外体 miR-23a 促进 M2 巨噬细胞极化并减轻心房纤维化。
