Glucagon-like peptide-1 receptor mediates the beneficial effect of liraglutide in an acute lung injury mouse model involving the thioredoxin-interacting protein
Autor: | Tianru Jin, Wenyong Zhou, Dinghui Liu, Yu Zhang, Mingyao Liu, Weijuan Shao |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Lipopolysaccharides Male Physiology Inflammasomes Endocrinology Diabetes and Metabolism medicine.medical_treatment Mice 0302 clinical medicine Thioredoxins Glucagon-Like Peptide 1 Receptor GLP-1R Mice Knockout medicine.diagnostic_test drug repurposing digestive oral and skin physiology Inflammasome Organ Size respiratory system TxNIP Cytokine Cytokines Bronchoalveolar Lavage Fluid TXNIP medicine.drug Research Article medicine.medical_specialty endocrine system LPS Thioredoxin-Interacting Protein Acute Lung Injury 030209 endocrinology & metabolism Lung injury Glucagon-Like Peptide-1 Receptor 03 medical and health sciences Physiology (medical) Internal medicine medicine Animals Hypoglycemic Agents Liraglutide business.industry Mice Inbred C57BL 030104 developmental biology Endocrinology Bronchoalveolar lavage business GLP-1 Carrier Proteins |
Zdroj: | American Journal of Physiology-Endocrinology and Metabolism |
ISSN: | 1522-1555 0193-1849 |
Popis: | Repurposing clinically used drugs is among the important strategies in drug discovery. Glucagon-like peptide-1 (GLP-1) and its diabetes-based drugs, such as liraglutide, possess a spectrum of extra-pancreatic functions, while GLP-1 receptor (GLP-1R) is most abundantly expressed in the lung. Recent studies have suggested that GLP-1-based drugs exert beneficial effects in chronic, as well as acute, lung injury rodent models. Here, we show that liraglutide pretreatment reduced LPS induced acute lung injury in mice. It significantly reduced lung injury score, wet/dry lung weight ratio, bronchoalveolar lavage fluid immune cell count and protein concentration, and cell apoptosis in the lung, and it was associated with reduced lung inflammatory cytokine and chemokine gene expression. Importantly, these effects were virtually absent in GLP-1R−/− mice. A well-known function of GLP-1 and GLP-based drugs in pancreatic β-cells is the attenuation of high-glucose stimulated expression of thioredoxin-interacting protein (TxNIP), a key component of inflammasome. LPS-challenged lungs showed elevated TxNIP mRNA and protein expression, which was attenuated by liraglutide treatment in a GLP-1R-dependent manner. Hence, our observations suggest that GLP-1R is essential in mediating beneficial effects of liraglutide in acute lung injury, with the inflammasome component TxNIP as a potential target. |
Databáze: | OpenAIRE |
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