LncRNA ANRIL Promotes Autophagy Activation Through miR-16-5p/TLR4 Axis in Allergic Rhinitis

Abstract

Background 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.

Updated epithelial barrier dysfunction in chronic rhinosinusitis: Targeting pathophysiology and treatment response of tight junctions

“…The localization of TJs in the normal nasal epithelium. As pro-inflammatory mediators, TNF reduces TER levels and expression of ZO-1 and occludin both in RPMI2650 cells, 98 inferior turbinate (IT) derived HNECs and BALB/c mice. 72 Despite IL-6 exhibited negligible influence on the barrier function of HNECs from NPs.…”

“…[148][149][150] Additionally, 3-methyladenine (an autophagy inhibitor) was found to ameliorate damage induced by TNF and Der p 1 in RPMI2650. 98,134 Furthermore, both histone deacetylase inhibitors 135,139 and cystatin aminotransferase inhibitors 142 could attenuate the effect of allergens on nasal epithelial barriers. Finally, inhibitors of signaling pathways (e.g., AKT, 149 MAPK, 112,120 and TLR 108 ) may also be potential targets for restoring TJs in nasal epithelial cells.…”

“…For example, N‐acetylcysteine (a reactive oxygen species inhibitor) has been shown to restore barrier function caused by PM 2.5 and PM 10 in RPMI2650 and primary HNECs (IT‐ and uncinate process‐derived) 148–150 . Additionally, 3‐methyladenine (an autophagy inhibitor) was found to ameliorate damage induced by TNF and Der p 1 in RPMI2650 98,134 . Furthermore, both histone deacetylase inhibitors 135,139 and cystatin aminotransferase inhibitors 142 could attenuate the effect of allergens on nasal epithelial barriers.…”

The Lifetime Pursuit of Solving Complex Questions

“…Allergic rhinitis and chronic sinusitis continue to grow in prevalence worldwide. Wang et al 1 help elucidate our understanding of the pathophysiology of allergic rhinitis (AR). Utilizing the ovalbumin-mice model, they demonstrate the LncRNA ANRIL pathway to upregulate autophagy and epithelial barrier dysfunction in the development of AR.…”