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

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

doi:10.1016/j.ejphar.2023.176185

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

Eur J Pharmacol. 2023 Dec 15:961:176185. doi: 10.1016/j.ejphar.2023.176185. Epub 2023 Nov 8.

Authors

Haixiong Tang¹, Zemin Chen², Sudan Gan², Yan Liang³, Hailing Zhang³, Changyun Yang², Liqin Lin², Yubiao Guo², Shiyue Li⁴, Jing Li⁵, Lihong Yao⁶

Affiliations

¹ Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
² Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
³ Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
⁴ Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address: lishiyue@188.com.
⁵ Department of Allergy and Clinical Immunology, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address: lijing@gird.cn.
⁶ Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, State Key Laboratory of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China. Electronic address: yaolh4321@126.com.

PMID: 37944848
DOI: 10.1016/j.ejphar.2023.176185

Abstract

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.

Keywords: Epithelium; GLUT1; Lung injury; Tight junctions.

MeSH terms

Acute Lung Injury* / chemically induced
Acute Lung Injury* / drug therapy
Acute Lung Injury* / metabolism
Animals
Glucose Transporter Type 1 / metabolism
Lipopolysaccharides / metabolism
Lipopolysaccharides / pharmacology
Mice
Occludin / metabolism
Tight Junction Proteins / metabolism
Tight Junctions*
Zonula Occludens-1 Protein / metabolism

Substances

WZB117
Occludin
Glucose Transporter Type 1
Lipopolysaccharides
Zonula Occludens-1 Protein
Tight Junction Proteins