Zhang Shitao, Dong Dong, Zhang Yuan, Wang Jia, Liu Lei, Zhao Yulin
Department of Rhinology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
Department of Rhinology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China.
Int Immunopharmacol. 2021 Dec;101(Pt B):108279. doi: 10.1016/j.intimp.2021.108279. Epub 2021 Oct 26.
MicroRNA-124-3p (miR-124-3p) and dipeptidyl peptidase-4 (DPP4) are closely related to the development of inflammation. Allergic rhinitis (AR) models in mice and HNEpC cells were established. AR progression was assessed assessing by the frequency of nasal rubbing and sneezing, hematoxylin and eosin (HE), and TUNEL staining. Tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), eotaxin, and MUC5AC were assessed by enzyme-linked immunosorbent assay and quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Apoptosis in HNEpC cells was assessed using flow cytometry. DPP4, activated-caspase-3, and pro-caspase-3 protein expression were evaluated by western blotting. In addition, we clarified the influence of miR-124-3p-targeted DPP4 on AR inflammation and cell injury. MiR-124-3p was downregulated in AR nasal mucosa tissue. Upregulation of miR-124-3p reduced the frequency of nasal rubbing and sneezing, pathological changes, eosinophil number, and apoptosis of nasal mucosa, TNF-α and IL-6 protein and mRNA levels in serum and HNEpC cells, and MUC5AC, eotaxin, and GM-CSF levels in HNEpC cells. Downregulation of miR-124-3p has the opposite effect. Therefore, the miR-124-3p /DPP4 axis may be an attractive target for AR therapy.
微小RNA-124-3p(miR-124-3p)和二肽基肽酶4(DPP4)与炎症的发展密切相关。建立了小鼠变应性鼻炎(AR)模型和人鼻上皮细胞(HNEpC)模型。通过鼻摩擦和打喷嚏的频率、苏木精-伊红(HE)染色和TUNEL染色评估AR进展。通过酶联免疫吸附测定和定量逆转录聚合酶链反应(qRT-PCR)评估肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)、粒细胞-巨噬细胞集落刺激因子(GM-CSF)、嗜酸性粒细胞趋化因子和黏蛋白5AC(MUC5AC)。使用流式细胞术评估HNEpC细胞中的凋亡。通过蛋白质印迹法评估DPP4、活化的半胱天冬酶-3和前半胱天冬酶-3蛋白表达。此外,我们阐明了miR-124-3p靶向的DPP4对AR炎症和细胞损伤的影响。miR-124-3p在AR鼻黏膜组织中表达下调。上调miR-124-3p可降低鼻摩擦和打喷嚏的频率、病理变化、嗜酸性粒细胞数量以及鼻黏膜的凋亡、血清和HNEpC细胞中TNF-α和IL-6蛋白及mRNA水平,以及HNEpC细胞中MUC5AC、嗜酸性粒细胞趋化因子和GM-CSF水平。下调miR-124-3p则产生相反的效果。因此,miR-124-3p/DPP4轴可能是AR治疗的一个有吸引力的靶点。