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 |
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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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