The role of miR-29c/B7-H3 axis in children with allergic asthma.
The role of miR-29c/B7-H3 axis in children with allergic asthma.
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miR-29c/B7-H3轴在儿童过敏性哮喘中的作用
DOI：
10.1186/s12967-018-1590-8
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发表时间：
2018-08-03
影响因子：
7.4
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Zhang X;Zhao X;Sun H;Yan Y;Huang L;Gu W;Jiang W;Wang Y;Zhu C;Ji W;Hao C;Chen Z
背景MicroRNAs在支气管哮喘的发病机制中发挥作用。然而，miR-29 c在过敏性哮喘中的作用机制尚不清楚。本研究旨在探讨单核巨噬细胞中miR-29 c对Th细胞分化的调控作用。从外周血中分离CD 14+单核细胞。使用微阵列分析评估microRNA的差异表达，并通过qRT-PCR测定单核细胞中的miR-29 c表达。用ELISA法测定血浆B7-H3。结果与对照组相比，哮喘患儿外周血单核细胞中88个miRNAs表达上调，41个miRNAs表达下调，其中miR-29 c表达上调的miRNAs占41个。哮喘急性发作组患儿血浆B7-H3水平显著高于对照组（P < 0.05），而miR-29 c水平显著低于对照组（P < 0.05）。基于荧光素酶报告基因分析和免疫荧光染色的功能研究表明，B7-H3是miR-29 c的直接靶点，转染抗miR-29 c的巨噬细胞可增强共培养的CD 4 +T细胞中ROR-γt和加塔-3的表达，并增加上清液中IL-4和IL-17的水平。H3通过调节Th 2/Th 17细胞分化在儿童哮喘中发挥重要作用，可能为哮喘的治疗提供新的靶点。
BackgroundMicroRNAs play roles in the pathogenesis of bronchial asthma. However, the mechanism of miR-29c in allergic asthma remains unclear. This study is to elucidate the regulation of Th cell differentiation by miR-29c in mononuclear macrophages.MethodsA total of 52 children with asthma exacerbation and 26 children as controls were enrolled in the study. CD14+monocytes were isolated from the peripheral blood. Differential expressions of microRNAs were evaluated using microarray analysis and miR-29c expression in monocytes was determined by qRT-PCR. The plasma B7-H3 was determined by ELISA. Transfection studies and luciferase reporter assay were performed to confirm target gene of miR-29c and its function.ResultsCompared to controls, 88 miRNAs in blood monocytes were up-regulated and 41 miRNAs down-regulated including miR-29c in asthma children. Children with asthma exacerbation had significantly lower level of miR-29c and higher level of plasma B7-H3 compared to controls (both P < 0.05). Functional studies based on luciferase reporter assay and immunofluorescence staining suggest that B7-H3 is the direct target of miR-29c and transfection anti-miR-29c into macrophages could enhance ROR-γt and GATA-3 expression in co-cultured CD4+T cells and increase levels of IL-4 and IL-17 in supernatants.ConclusionThe axis of miR-29c/B7-H3 plays an important role in children with asthma through regulating Th2/Th17 cell differentiation and may provide new targets for treatment of asthma.
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DOI：
10.4049/jimmunol.0803560
发表时间：
2009-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lu TX;Munitz A;Rothenberg ME
通讯作者：
Rothenberg ME
DOI：
10.1183/09031936.00068712
发表时间：
2014-03
期刊：
The European respiratory journal
影响因子：
--
作者：
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通讯作者：
Kraft M
DOI：
10.1038/nri3494
发表时间：
2013-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.8
作者：
Frieri, Marianne
通讯作者：
Frieri, Marianne
影响因子：
24.3
作者：
Chung, Kian Fan;Wenzel, Sally E.;Teague, W. Gerald
通讯作者：
Teague, W. Gerald