Role of A2B adenosine receptor-dependent adenosine signaling in multi-walled carbon nanotube-triggered lung fibrosis in mice

Autor: Zhigang Zhang, Biying Liu, Bing Han, Jingjing Lu, Siyu Li, Ruiqi Baiyun, Yueying Lv, Qizheng Bing, Xiaoya Zhang, Hao Wu
Rok vydání: 2019
Předmět:
Male
Adenosine
Pulmonary Fibrosis
Pharmaceutical Science
Medicine (miscellaneous)
Multi-walled carbon nanotubes
02 engineering and technology
01 natural sciences
Applied Microbiology and Biotechnology
Fibrosis
Lung
medicine.diagnostic_test
biology
Chemistry
Cell Differentiation
021001 nanoscience & nanotechnology
High-performance liquid chromatography
Adenosine A2 Receptor Antagonists
lcsh:R855-855.5
Myeloperoxidase
Molecular Medicine
Collagen
0210 nano-technology
Myofibroblast
Signal Transduction
medicine.drug
lcsh:Medical technology
Follistatin-Related Proteins
Cell Survival
lcsh:Biotechnology
A2B adenosine receptor
Biomedical Engineering
Bioengineering
Receptor
Adenosine A2B
010402 general chemistry
Transforming Growth Factor beta1
lcsh:TP248.13-248.65
Follistatin-like 1
medicine
Extracellular
Animals
Fibroblast-to-myofibroblast transition
Peroxidase
Nanotubes
Carbon
Research
Fibroblasts
medicine.disease
Adenosine receptor
0104 chemical sciences
Mice
Inbred C57BL
Bronchoalveolar lavage
Purines
Cancer research
biology.protein
Pyrazoles
Lung fibrosis
Transforming growth factor-β1
Transforming growth factor
Zdroj: Journal of Nanobiotechnology
Journal of Nanobiotechnology, Vol 17, Iss 1, Pp 1-11 (2019)
ISSN: 1477-3155
Popis: Background Multi-walled carbon nanotube (MWCNT)-induced lung fibrosis leads to health concerns in human. However, the mechanisms underlying fibrosis pathogenesis remains unclear. The adenosine (ADO) is produced in response to injury and serves a detrimental role in lung fibrosis. In this study, we aimed to explore the ADO signaling in the progression of lung fibrosis induced by MWCNT. Results MWCNT exposure markedly increased A2B adenosine receptor (A2BAR) expression in the lungs and ADO level in bronchoalveolar lavage fluid, combined with elevation of blood neutrophils, collagen fiber deposition, and activation of myeloperoxidase (MPO) activity in the lungs. Furthermore, MWCNT exposure elicited an activation of transforming growth factor (TGF)-β1 and follistatin-like 1 (Fstl1), leading to fibroblasts recruitment and differentiation into myofibroblasts in the lungs in an A2BAR-dependent manner. Conversely, treatment of the selective A2BAR antagonist CVT-6883 exhibited a significant reduction in levels of fibrosis mediators and efficiently decreased cytotoxicity and inflammatory in MWCNT treated mice. Conclusion Our results reveal that accumulation of extracellular ADO promotes the process of the fibroblast-to-myofibroblast transition via A2BAR/TGF-β1/Fstl1 signaling in MWCNT-induced lung fibrosis.
Databáze: OpenAIRE
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