GBP2 Regulates Lipid Metabolism by Inhibiting the HIF-1 Pathway to Alleviate the Progression of Allergic Rhinitis.

Abstract

Allergic rhinitis (AR) is a prevalent allergic disorder instigated by a variety of allergenic stimuli. The study aims to elucidate the mechanistic underpinnings of Guanylate-binding protein 2 (GBP2) in modulating AR. Bioinformatics analysis was used to identify hub genes in AR, and GBP2 was identified. Mice were injected with ovalbumin (OVA) to create AR model. The pathological changes of the nasal mucosa were observed by hematoxylin-eosin staining. ELISA and western blot demonstrated that in OVA-induced AR mice, high IgE and IgG1 levels, inflammation (increased TNF-α, IL-5 and IFN-γ), oxidative stress (high ROS, low TAOC and GSH) and abnormal lipid metabolism (increased TC and LDL-C, decreased HLD-C) were observed. Mouse nasal mucosal epithelial cells (MNECs) were treated with TNF-α to simulate AR. Cell viability and apoptosis were evaluated by CCK-8 assay and flow cytometer, respectively. In vitro assay revealed that GBP2 inhibited total IgE, OVA-IgE and IgG1 levels and suppressed abnormal lipid metabolism, inflammation and oxidative stress to alleviate AR. Furthermore, HIF-1 pathway was screened as the downstream pathway of GBP2. GBP2 inhibited the HIF-1 pathway, and Fenbendazole-d3, the activator of HIF-1 pathway, weakened the inhibitory effects of GBP2 on apoptosis, inflammation, oxidative stress and abnormal lipid metabolism in vitro. In summary, GBP2 alleviated abnormal lipid metabolism, inflammation and oxidative stress by inhibiting the HIF-1 pathway, providing a direction for the treatment of AR.