Glucagon-like peptide-1 receptor activation alleviates lipopolysaccharide-induced acute lung injury in mice via maintenance of endothelial barrier function.

Abstract

Glucagon-like peptide-1 (GLP-1), which is well known for regulating glucose homeostasis, exhibits multiple actions in cardiovascular disorders and renal injury. However, little is known about the effect of GLP-1 receptor (GLP-1R) activation on acute lung injury (ALI). In this study, we investigated the effect of GLP-1R on ALI and the potential underlying mechanisms with the selective agonist liraglutide. Our results show that GLP-1 levels decreased in serum, though they increased in bronchoalveolar lavage fluid (BALF) and lung tissue in a mouse model of lipopolysaccharide (LPS)-induced ALI. Liraglutide prevented LPS-induced polymorphonuclear neutrophil (PMN) extravasation, lung injury, and alveolar-capillary barrier dysfunction. In cultured human pulmonary microvascular endothelial cells (HPMECs), liraglutide protected against LPS-induced endothelial barrier injury by restoring intercellular tight junctions and adherens junctions. Moreover, liraglutide prevented PMN-endothelial adhesion by inhibiting the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and thereafter suppressed PMN transendothelial migration. Furthermore, liraglutide suppressed LPS-induced activation of Rho/NF-κB signaling in HPMECs. In conclusion, our results show that GLP-1R activation protects mice from LPS-induced ALI by maintaining functional endothelial barrier and inhibiting PMN extravasation. These results also suggest that GLP-1R may be a potential therapeutic target for the treatment of ALI.

• Authors: Jian Xu, Guihong Wei, Jingjing Wang, Jiali Zhu, Min Yu, Xiaoning Zeng, Hong Wang, Weiping Xie, Hui Kong
• Journal: Laboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 99 Issue 4 Pg. 577-587 (04 2019) ISSN: 1530-0307 [Electronic] United States
• PMID: 30659271 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucagon-Like Peptide-1 Receptor
• Lipopolysaccharides
• Liraglutide

Topics

• Acute Lung Injury (chemically induced, metabolism)
• Animals
• Cell Line
• Endothelial Cells (cytology, drug effects, physiology)
• Glucagon-Like Peptide-1 Receptor (agonists, metabolism)
• Humans
• Lipopolysaccharides (adverse effects)
• Liraglutide (pharmacology)
• Male
• Mice
• Signal Transduction (drug effects)