GLUT3 mediated airway remodeling in chronic obstructive pulmonary disease through the NF-kB/ZEB1 pathway

Airway remodeling plays an important role in the pathogenesis of COPD. More and more evidence suggest that GLUT3 is involved in the epithelial mesenchymal transition (EMT) process of various diseases. However, the role of GLUT3 in EMT in airway epithelial cells of COPD patients is still unclear. We detected the levels of GLUT3 in peripheral lung tissue of COPD patients and cigarette smoke exposed mice. Two GEO datasets were utilized to analyse GLUT3 gene expression profiles in COPD. Western blot and immunofluorescence were used to detect the expression of GLUT3. A cell study was performed to confirm the regulatory effect of GLUT3. Inhibition of GLUT3 expression with siRNA, Western blot and immunofluorescence methods were used to detect the expression of E-cadherin, N-cadherin, vimentin, p65 and ZEB1. In addition, Masson’s staining and lung fuction measurement were used detect the collagen deposition and the penh of mice. Based on Gene Expression Omnibus (GEO) data set analysis, GLUT3 expression in COPD patients was higher than in non-smokers. Moreover,GLUT3 was highly expressed in COPD patients, CS exposed mice, and BEAS-2B cells treated with CS extract (CSE). Further research has found that down-regulation of GLUT3 significantly alleviate airway remodeling in vivo and in vitro. Lung function measurement showed that the reduction of GLUT3 reduced the airway resistance in experimental COPD mice. Mechanistically, our study showed that reduction of GLUT3 inhibited CSE-induced EMT by down-regulated the NF-κB/ZEB1 pathway. These findings uncover a key role of GLUT3 in modulating the airway remodeling and shed light on the development of GLUT3-targeted therapeutics for COPD.