GBP2 通过抑制 HIF-1 通路调节脂质代谢以缓解过敏性鼻炎的恶化

IF 1.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yunsong An, Jun Xu, Xiaoqi Hu, MiMi Xu, Xuechun Yang, Tao Liu
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引用次数: 0

摘要

过敏性鼻炎(AR)是由多种过敏原刺激引发的一种普遍过敏性疾病。本研究旨在阐明鸟苷酸结合蛋白 2(GBP2)调节 AR 的机制基础。研究人员利用生物信息学分析确定了 AR 的枢纽基因,并确定了 GBP2。给小鼠注射卵清蛋白(OVA)建立AR模型。通过苏木精-伊红染色观察鼻粘膜的病理变化。酶联免疫吸附试验(ELISA)和免疫印迹(Western blot)表明,在卵清蛋白诱导的AR小鼠中,观察到高IgE和IgG1水平、炎症(TNF-α、IL-5和IFN-γ增加)、氧化应激(高ROS、低TAOC和GSH)和脂质代谢异常(TC和LDL-C增加,HLD-C减少)。用 TNF-α 处理小鼠鼻黏膜上皮细胞(MNECs)以模拟 AR。细胞活力和细胞凋亡分别通过 CCK-8 检测法和流式细胞仪进行评估。体外实验显示,GBP2 可抑制总 IgE、OVA-IgE 和 IgG1 水平,抑制异常脂质代谢、炎症和氧化应激,从而缓解 AR。此外,GBP2 的下游通路是 HIF-1。GBP2 可抑制 HIF-1 通路,而 HIF-1 通路的激活剂芬苯达唑-d3 可削弱 GBP2 对体外细胞凋亡、炎症、氧化应激和异常脂质代谢的抑制作用。总之,GBP2通过抑制HIF-1通路缓解了脂质代谢异常、炎症和氧化应激,为AR的治疗提供了一个方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
GBP2 Regulates Lipid Metabolism by Inhibiting the HIF-1 Pathway to Alleviate the Progression of Allergic Rhinitis.

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.

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来源期刊
Cell Biochemistry and Biophysics
Cell Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
4.40
自引率
0.00%
发文量
72
审稿时长
7.5 months
期刊介绍: Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.
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