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Mesenchymal Stem Cell-Derived Exosome-Containing Linc00632 Regulates GATA Binding Protein-3 Expression in Allergic Rhinitis by Interacting with Enhancer of Zeste Homolog 2 to Inhibit T Helper Cell 2 Differentiation
International Archives of Allergy and Immunology ( IF 2.5 ) Pub Date : 2021-09-17 , DOI: 10.1159/000518950
Wei Li 1 , Cui-Yun Cai 1 , Jun-Jie Zeng 1
Affiliation  

Background: Allergic rhinitis (AR) is regarded as one of the most common allergic disease of nasal mucosa affecting many people worldwide. Long noncoding RNAs are critical modulators affecting AR progression, whereas the pathogenesis of Linc00632 in the development of AR remains unclear. Methods: T helper cell 2 (Th2) differentiation of CD4+ T cells was measured by flow cytometry. Real-time quantitative PCR assay and Western blot were applied to determine the levels of RNA and proteins, respectively. The interleukin (IL)-4 and IL-13 levels were quantitatively assessed through ELISA. Subcellular fractionation was conducted to detect the cellular localization of Linc00632. RNA immunoprecipitation experiment was employed to validate the interaction relationship between Linc00632 and enhancer of zeste homolog 2 (EZH2). Chromatin immunoprecipitation assay was used for determination of protein-DNA interactions. Results: The expression of Linc00632 was significantly decreased by 4 times in nasal mucosa of AR patients. Human umbilical cord mesenchymal stem cell-derived exosome dramatically inhibited Th2 differentiation, decreased GATA binding protein-3 (GATA-3) protein expressions and IL-4 levels by about 2 times in CD4+ T cells. Knockdown Linc00632 partially reversed the effects of exosomes on Th2 differentiation, IL-4 and IL-13 levels, and GATA-3 expression. Linc00632 overexpression could suppress Th2 differentiation of CD4+ T cells, reduced IL-4 and IL-13 levels, and GATA-3 expressions roughly 2 times. Linc00632 repressed the expression of GATA-3 by interacting with EZH2. GATA-3 overexpression partially reversed the effect of Linc00632 on Th2 differentiation of CD4+ T cells. Conclusion: Linc00632 acted as a suppression factor in Th2 differentiation by inhibiting the expression of GATA-3 via interacting with EZH2, which might provide a new insight for understanding the action mechanism of Linc00632 in AR.
Int Arch Allergy Immunol


中文翻译:

间充质干细胞衍生的含有 Linc00632 的外泌体通过与 Zeste 同源物 2 增强剂相互作用抑制 T 辅助细胞 2 分化来调节过敏性鼻炎中 GATA 结合蛋白 3 的表达

背景:过敏性鼻炎(AR)被认为是影响全世界许多人的最常见的鼻粘膜过敏性疾病之一。长非编码RNA是影响AR进展的关键调节剂,而Linc00632在AR发展中的发病机制仍不清楚。方法:通过流式细胞术测量CD4 + T 细胞的 T 辅助细胞 2 (Th2) 分化应用实时定量PCR测定和Western blot分别测定RNA和蛋白质的水平。通过 ELISA 定量评估白细胞介素 (IL)-4 和 IL-13 水平。进行亚细胞分级分离以检测Linc00632的细胞定位。采用RNA免疫沉淀实验验证Linc00632与zeste同源物增强子2(EZH2)之间的相互作用关系。染色质免疫沉淀测定用于测定蛋白质-DNA 相互作用。结果: AR患者鼻粘膜中Linc00632的表达显着降低4倍。人脐带间充质干细胞来源的外泌体显着抑制 Th2 分化,使 CD4 + T 细胞中的 GATA 结合蛋白-3 (GATA-3) 蛋白表达和 IL-4 水平降低约 2 倍。敲除 Linc00632 部分逆转了外泌体对 Th2 分化、IL-4 和 IL-13 水平以及 GATA-3 表达的影响。Linc00632过表达可以抑制CD4 + T细胞的Th2分化,降低IL-4和IL-13水平以及GATA-3表达约2倍。Linc00632 通过与 EZH2 相互作用抑制 GATA-3 的表达。GATA-3 过表达部分逆转了 Linc00632 对 CD4 + T 细胞Th2 分化的影响。结论: Linc00632通过与EZH2相互作用抑制GATA-3的表达,从而发挥Th2分化抑制因子的作用,这可能为理解Linc00632在AR中的作用机制提供新的见解。
Int Arch 过敏免疫
更新日期:2021-09-17
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