MicroRNAs (miRNAs) are a class of short non-coding RNAs that play a significant role in biological processes in various cell types, including mesenchymal stem cells (MSCs). However, how miRNAs regulate the immunomodulatory functions of adipose-derived MSCs (AD-MSCs) remains unknown. Here, we showed that modulation of miR-301a in AD-MSCs altered macrophage polarization. Bone marrow (BM)-derived macrophages were stimulated with LPS (1 μg/ml) and co-cultured with miRNA transfected AD-MSCs for 24 h. The expression of M1 and M2 markers in macrophages was analyzed. Inhibition of miR-301a induced M2 macrophage with arginase-1, CD163, CD206, and IL-10 upregulation. Additionally, toll-like receptor (TLR)-4 mRNA expression in macrophages was downregulated in co-cultures with AD-MSCs transfected with a miR-301a inhibitor. Nitric oxide (NO) in the supernatant of AD-MSC/macrophage co-culture was also suppressed by inhibition of miR-301a in AD-MSCs. We further found that suppression of miR-301a in AD-MSCs increased prostaglandin E₂ (PGE2) concentration in the conditioned medium of the co-culture. Taken together, the results of our study indicate that miR-301a can modulate the immunoregulatory functions of AD-MSCs that favor the applicability as a potential immunotherapeutic agent.

MicroRNA (miRNA) 是一类短的非编码 RNA，在包括间充质干细胞 (MSC) 在内的各种细胞类型的生物过程中发挥着重要作用。然而，miRNAs 如何调节脂肪来源的 MSCs (AD-MSCs) 的免疫调节功能仍然未知。在这里，我们表明 AD-MSC 中 miR-301a 的调​​节改变了巨噬细胞极化。骨髓 (BM) 衍生的巨噬细胞用 LPS (1 μg/ml) 刺激，并与 miRNA 转染的 AD-MSCs 共培养 24 小时。分析了巨噬细胞中 M1 和 M2 标志物的表达。抑制 miR-301a 诱导 M2 巨噬细胞，精氨酸酶-1、CD163、CD206 和 IL-10 上调。此外，在与转染 miR-301a 抑制剂的 AD-MSC 共培养中，巨噬细胞中的 Toll 样受体 (TLR)-4 mRNA 表达下调。AD-MSC/巨噬细胞共培养物上清液中的一氧化氮 (NO) 也被 AD-MSC 中 miR-301a 的抑制所抑制。我们进一步发现 AD-MSCs 中 miR-301a 的抑制增加了前列腺素 E₂ (PGE2) 在共培养条件培养基中的浓度。总之，我们的研究结果表明 miR-301a 可以调节 AD-MSCs 的免疫调节功能，有利于作为潜在的免疫治疗剂的适用性。