GLUT1 contributes to impaired epithelial tight junction in the late phase of acute lung injury

作者：Tang, Haixiong; Chen, Zemin; Gan, Sudan; Liang, Yan; Zhang, Hailing; Yang, Changyun; Lin, Liqin; Guo, Yubiao; Li, Shiyue^*; Li, Jing^*; Yao, Lihong^*

来源：European Journal of Pharmacology, 2023, 961: 176185.

DOI：10.1016/j.ejphar.2023.176185

• Lung injury
• Epithelium
• GLUT1
• Tight junctions

Dysfunction of epithelial barrier is crucial for the development of acute lung injury (ALI). This study was aimed to evaluate the role of glucose transporter 1 (GLUT1) in dysregulation of epithelial tight junction in ALI. GLUT1 was inhibited with specific antagonists WZB117 or BAY876 to see the effects on epithelial tight junction in a well-established LPS-induced mouse ALI model as well as in vitro cultured epithelial cells. Pharmacological inhibition of GLUT1 with WZB117 at either a low or high dose had no effects on lung injury and inflammation 24 h after LPS challenge, but significantly decreased the pulmonary inflammatory responses induced by LPS at 72 h with a high dose, which was verified by treatment with BAY876. WZB117 or BAY876 also recovered the expression of epithelial tight junction proteins ZO-1 and occludin. In cultured BEAS-2B and A549 cells, LPS induced increased GLUT1 expression, accompanied by decreased expression of tight junction protein ZO-1 and occludin. Blockade of GLUT1 restored LPS-induced disruption of ZO-1 and occludin in BEAS-2B rather than A549. Taken together, our results showed that GLUT1 is responsible for dysfunction of epithelial tight junctions in the late phase of LPS-induced ALI.

• 单位
  1; 广州医学院; 南方医科大学