Hexokinase 2 aggravates airway inflammation in experimental asthma by regulating airway epithelial cell death

Abstract

Abstract Background Asthma is a prevalent inflammatory lungs disease which poses a substantial global health and economic burden. Abnormal glucose metabolism in asthmatic patients has recently attracted much attention. As a key enzyme in glycolysis, the participation of Hexokinase 2(HK2) in the disease course of asthma has not been fully understudied. Methods In an asthma mouse model, the expression levels of Hexokinase 2 (HK2) were validated, and a mouse model with HK2 specifically knocked out in airway epithelial cells was created to investigate the role of HK2 in bronchial asthma. In vitro cellular experiments involved the overexpression and knockdown of HK2 to study its role and related mechanisms in airway epithelial cell death and airway inflammation in bronchial asthma. Results HK2 is found to have increased expression in both mouse asthma models, especially showing elevated expression in airway epithelial cells. Mice that specifically lacked HK2 in their airway epithelium were observed to be protected from cell death and inflammation during asthma. Moreover, airway epithelial cells treated with HK2 overexpression exacerbated cell death and elevated the expression of inflammatory interleukins, conversely after silencing HK2 in vitro, cell death and inflammatory interleukins expression were greatly improved. We further surmise that HK2 might be involved in the regulation of airway epithelial cell death and airway inflammation through PPIF and VDAC1. Furthermore, the treatment of mice with HK2 inhibitor, 2-DG, markedly attenuated the inflammatory cell infiltration in the pulmonary tissues. Conclusion HK2 plays a crucial role in the occurrence and progression of bronchial asthma, being involved in airway epithelial cell death and airway inflammation.