The role of miR-29c/B7-H3 axis in children with allergic asthma

miR-29c/B7-H3轴在儿童过敏性哮喘中的作用

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作者:Xinxing Zhang, Xin Zhao, Huiming Sun, Yongdong Yan, Li Huang, Wenjin Gu, Wujun Jiang, Yuqing Wang, Canhong Zhu, Wei Ji, Chuangli Hao, Zhengrong Chen

Background

MicroRNAs 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.

Conclusion

The 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.

Methods

A 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.

Results

Compared 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.

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