Department of Otorhinolaryngology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China.
Department of Rehabilitation Medicine, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, China.
Kaohsiung J Med Sci. 2022 Apr;38(4):347-356. doi: 10.1002/kjm2.12487. Epub 2022 Jan 10.
Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa. M2 macrophage polarization can reduce inflammation and repair tissue injury during AR development. Studies have substantiated the involvement of miRNAs in AR pathogenesis. Herein, the molecular mechanism of miR-214-3p in AR development was explored. To mimic the AR environment, ovalbumin (OVA) was used to treat macrophages. MiR-214-3p and glycogen synthase kinase 3 beta (GSK3B) expression in nasal mucus tissues and macrophages was assessed by RT-qPCR. The M2 phenotypic signature of CD206 in macrophages was assessed by flow cytometry. The protein expression of GSK3B and M2 macrophage markers (ARG-1 and IL-10) was evaluated by western blotting. The correlation between miR-214-3p and GSK3B was validated by a luciferase reporter assay. We found that miR-214-3p was overexpressed in macrophages and nasal mucus tissues from AR patients. MiR-214-3p facilitated M2 polarization of macrophages upon OVA stimulation. Mechanistically, miR-214-3p targeted the GSK3B 3' untranslated region in macrophages. In addition, GSK3B was downregulated in macrophages and nasal mucus tissues from AR patients. In rescue assays, GSK3B downregulation reversed the inhibitory effects of miR-214-3p silencing on M2 polarization of macrophages treated with OVA. Overall, miR-214-3p facilitates M2 macrophage polarization by targeting GSK3B.
变应性鼻炎（AR）是一种鼻黏膜的慢性炎症性疾病。M2 巨噬细胞极化在 AR 发展过程中可以减轻炎症和修复组织损伤。研究已经证实 miRNA 参与了 AR 的发病机制。在此，探讨了 miR-214-3p 在 AR 发展中的分子机制。为了模拟 AR 环境，使用卵清蛋白（OVA）处理巨噬细胞。通过 RT-qPCR 评估鼻黏液组织和巨噬细胞中 miR-214-3p 和糖原合酶激酶 3β（GSK3β）的表达。通过流式细胞术评估巨噬细胞中 CD206 的 M2 表型特征。通过 Western blot 评估 GSK3β 和 M2 巨噬细胞标志物（ARG-1 和 IL-10）的蛋白表达。通过荧光素酶报告基因测定验证 miR-214-3p 和 GSK3β 之间的相关性。我们发现 miR-214-3p 在 AR 患者的巨噬细胞和鼻黏液组织中过度表达。miR-214-3p 促进 OVA 刺激后的巨噬细胞 M2 极化。在机制上，miR-214-3p 靶向巨噬细胞中的 GSK3β 3'非翻译区。此外，在 AR 患者的巨噬细胞和鼻黏液组织中，GSK3β 下调。在挽救实验中，GSK3β 下调逆转了 miR-214-3p 沉默对 OVA 处理的巨噬细胞 M2 极化的抑制作用。总之，miR-214-3p 通过靶向 GSK3β 促进 M2 巨噬细胞极化。
