Department of Ophthalmology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea.
Department of Ophthalmology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul 03080, Korea.
Int J Mol Sci. 2020 Sep 16;21(18):6809. doi: 10.3390/ijms21186809.
Mounting evidence indicates that microRNAs (miRNAs), including miR-146a, have an impact on the immunomodulatory activities of mesenchymal stem/stromal cells (MSCs). Suppression of inflammatory macrophage activation is one of the main immunomodulatory mechanisms of MSCs. Here, we investigated whether miR-146a in MSCs might play a role in the effects of MSCs on macrophage activation. A miRNA microarray revealed that miR-146a was the most highly upregulated miRNA in MSCs upon co-culture with activated macrophages. Inhibition of miR-146a in MSCs through miR-146a inhibitor transfection had a different effect on the expression of immunoregulatory factors secreted by MSCs. Pentraxin 3, tumor necrosis factor-inducible gene 6, and cyclooxygenase-2, which are well-known mediators of the immunomodulatory functions of MSCs, were significantly upregulated in MSCs after miR-146a knockdown. By contrast, hepatocyte growth factor and stanniocalcin 1, other immunoregulatory molecules expressed by MSCs, were downregulated by miR-146a knockdown. Consequently, the inhibition of miR-146a in MSCs did not change the overall effect of MSCs on the suppression of inflammatory macrophage activation or the induction of anti-inflammatory macrophage polarization.
越来越多的证据表明，微小 RNA（miRNA），包括 miR-146a，对间充质干细胞（MSCs）的免疫调节活性有影响。抑制炎症性巨噬细胞的激活是 MSCs 主要的免疫调节机制之一。在这里，我们研究了 MSCs 中的 miR-146a 是否可能在 MSCs 对巨噬细胞激活的影响中发挥作用。miRNA 微阵列显示，在与激活的巨噬细胞共培养时，miR-146a 是 MSC 中上调最明显的 miRNA。通过 miR-146a 抑制剂转染抑制 MSC 中的 miR-146a 对 MSC 分泌的免疫调节因子的表达有不同的影响。众所周知，MSC 免疫调节功能的调节因子，如 pentraxin 3、肿瘤坏死因子诱导基因 6 和环氧化酶-2，在 miR-146a 敲低的 MSC 中显著上调。相比之下，miR-146a 敲低下调了 MSC 表达的其他免疫调节分子，如肝细胞生长因子和 stanniocalcin 1。因此，抑制 MSC 中的 miR-146a 并没有改变 MSC 对抑制炎症性巨噬细胞激活或诱导抗炎性巨噬细胞极化的整体影响。
