期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 83, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2020.106475
关键词
Asthma; Airway smooth muscle cells; TNF-alpha; TRIM8; miR-182-5p
资金
- International Science and Technology Cooperation and Communication Project of Shaanxi Province [2020KW-046]
- Interdisciplinary Subjects of Special Funds of Fundamental Research Funds for the Central Universities [10698201358]
MicroRNAs (miRNAs) have emerged as critical modulators involved in the regulation of airway remodeling in asthma. MicroRNA-182-5p (miR-182-5p) has been reported as a key miRNA in regulating the proliferation and migration of various cell types, and its dysfunction contributes is implicated in a wide range of pathological processes. Yet, it remains unknown whether miR-182-5p modulates the proliferation and migration of airway smooth muscle (ASM) cells during asthma. In the present study, we aimed to determine the potential role of miR-182-5p in regulating the proliferation and migration of ASM cells induced by tumor necrosis factor (TNF)-alpha in vitro. We found that TNF-alpha stimulation markedly reduced miR-182-5p expression in ASM cells. Gain-of-function experiments showed that miR-182-5p upregulation suppressed the proliferation and migration of ASM cells induced by TNF-alpha. By contrast, miR-182-5p inhibition had the opposite effect. Notably, tripartite motif 8 (TRIM8) was identified as a target gene of miR-182-5p. TRIM8 expression was induced by TNF-alpha stimulation, and TRIM8 knockdown markedly impeded TNF-alpha-induced ASM cell proliferation and migration. Moreover, miR-182-5p overexpression or TRIM8 knockdown significantly downregulated the activation of nuclear factor-kappa B (NF-kappa B) induced by TNF-alpha. However, TRIM8 restoration partially reversed the miR-182-5p-mediated inhibitory effect on TNF-alpha-induced ASM cell proliferation and migration. In conclusion, our study indicates that miR-182-5p restricts TNF-alpha-induced ASM cell proliferation and migration through downregulation of NF-kappa B activation via targeting TRIM8. The results of our study highlight the potential importance of the miR-182-5p/TRIM8/NF-kappa B axis in the airway remodeling of asthma.
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