Allergic rhinitis (AR) is an allergic disease of nasal mucosa. LncRNAs are key modulators affecting AR development. Neverthelss, the impact of lncRNA ANRIL in AR is not clear.
Objective
This work decided to study the mechanism underlying the impact of ANRIL on TLR4 expression through targeting miR-16-5p during autophagy and epithelial barrier dysfunction in the progression of AR.
Methods
Human nasal epithelial cells were exposed to TNF-α to establish AR cell model, AR mice model was constructed by ovalbumin (OVA) treatment. QRT-PCR or western blot assays were applied to measure the levels of mRNA and proteins. Dual-luciferase reporter gene detection and RIP assay were conducted to verify the association between ANRIL and miR-16-5p. Autophagy flux assessment by mRFP-GFP-LC3 method was performed to detect autophagy level.
Results
AR progression could induce the autophagy, and the expressions of tight junction proteins were downregulated in AR cell model. Moreover, knockdown of ANRIL reversed the effect of AR on autophagy-related protein and tight junction proteins MiR-16-5p was found to be bound with ANRIL and miR-16-5p inhibitor could reverse ANRIL knockdown-induced downregulation of autophagy-related proteins and epithelial barrier dysfunction. In addition, miR-16-5p directly targeted TLR4. Furthermore, knockdown of ANRIL reversed miR-16-5p and TLR4 expression, autophagy level, and tight junction protein levels in nasal mucosa of AR mice.
Conclusion
This study illustrated that ANRIL acted as a promotion factor in AR induced autophagy and epithelial barrier dysfunction by enhancing the expression of TLR4 via interacting with miR-16-5p.
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