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
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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