Inhibiting lncRNA SNHG5 alleviates the inflammatory response in eosinophilic chronic rhinosinusitis with nasal polyps by regulating the miR-489/TLR4/NF-κB pathway

Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP), a major subtype of chronic rhinosinusitis (CRS), is a heterogeneous and multifactorial disease correlated with T2 inflammatory response. In recent years, long noncoding RNAs (lncRNAs) have garnered increasing attention due to their regulatory roles in various inflammatory diseases. This research aims to explore the effects of a specific lncRNA, SNHG5, on the inflammatory response of mast cells in ECRSwNP and the underlying molecular mechanism. The expression and effect of SNHG5 were initially assessed in the nasal mucosal tissue of the CRSwNP mouse model and an ovalbumin (OVA)-induced activated mast cell line (MC/9 cells). The underlying mechanisms were further investigated and verified using RT-PCR, Western blot, H&E, immunofluorescence staining, etc. Here, we found that the expression level of SNHG5 was significantly upregulated in ECRSwNP. In vitro, the knockdown of SNHG5 decreased the proliferation of activated MC/9 cells and the production of inflammatory cytokines. In vivo , the downregulation of SNHG5 alleviated nasal mucosal lesions and decreased the levels of Th2-specific cytokines in nasal mucosal tissues. Moreover, it was found that SNHG5 binds to miR-489-3p, thereby inhibiting the TLR4/MyD88/NF-κB p65 signaling pathway. Notably, suppression of miR-489-3p could reverse the protective effect of SNHG5 downregulation on the inflammatory response both inflammatory response in vivo and in vitro . Taken together, this study reveals that lncRNA SNHG5 may be involved in the inflammatory response of mast cells in ECRSwNP through the miR-489-3p-mediated TLR4/NF-κB signaling pathway.inflammatory response, probably offering a new potential therapy target for CRSwNP.