A study of Tian Zhen in asthma

Hexokinase catalyzes the initial rate-limiting step in glucose metabolism by transforming glucose into glucose-6-phosphate. However, the roles of hexokinase 2(HK2) in asthma remain incompletely understood. This study aimed to investigate metabolic alterations in asthma, focusing on the expression, function and regulation of HK2. Analysis of non-targeted metabolomics revealed metabolic alterations in asthma, particularly in glycolysis pathway. HK2 expression was elevated in both asthma individuals and murine models. Airway epithelium–specific-HK2-knockdown alleviated airway inflammation and hyperresponsiveness in asthmatic murine models. Moreover, HK2 regulated epithelial apoptosis and inflammation interacting with peptidyl-prolyl cis-trans isomerase (PPIF) but not voltage-dependent anion channel 1(VDAC1). Moreover, inhibiting HK2 with 2-DG significantly alleviated airway inflammation and hyperresponsiveness. Asthma is associated with metabolic reprogramming, characterized by alterations in lipid and glucose metabolism. HK2 plays a crucial role in asthma pathogenesis by promoting airway epithelial apoptosis and inflammation via PPIF. Targeting HK2 represents a promising therapeutic strategy for asthma treatment.己糖激酶（Hexokinase）可将葡萄糖转化为葡萄糖-6-磷酸，催化葡萄糖代谢中的初始限速步骤。然而，己糖激酶2（hexokinase 2, HK2）在哮喘中的作用仍未完全阐明。本研究旨在探讨哮喘中的代谢改变，重点关注HK2的表达、功能及其调控机制。非靶向代谢组学分析显示，哮喘患者与小鼠模型体内均存在代谢改变，尤以糖酵解通路最为显著。哮喘患者与小鼠模型中HK2的表达均上调。气道上皮特异性HK2敲低可减轻哮喘小鼠模型的气道炎症与气道高反应性。此外，HK2可通过与肽基脯氨酰顺反异构酶（peptidyl-prolyl cis-trans isomerase, PPIF）相互作用调控上皮细胞凋亡与炎症，而非与电压依赖性阴离子通道1（voltage-dependent anion channel 1, VDAC1）结合。此外，使用2-脱氧葡萄糖（2-DG）抑制HK2可显著减轻气道炎症与气道高反应性。哮喘与代谢重编程相关，其特征为脂质代谢与葡萄糖代谢发生改变。HK2可通过PPIF介导气道上皮细胞凋亡与炎症，在哮喘发病机制中发挥关键作用。靶向HK2有望成为哮喘治疗的潜在治疗策略。