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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Biying Liu, Qizheng Bing, Siyu Li, Bing Han, Jingjing Lu, Ruiqi Baiyun, Xiaoya Zhang, Yueying Lv, Hao Wu, Zhigang Zhang

ABSTRACT

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. More... »

PAGES

45

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12951-019-0478-y

DOI

http://dx.doi.org/10.1186/s12951-019-0478-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1113058189

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30922349


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