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

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

  • J Nanobiotechnology. 2019 Mar 29;17(1):45. doi: 10.1186/s12951-019-0478-y.
Biying Liu 1 2 Qizheng Bing 1 2 Siyu Li 1 2 Bing Han 1 Jingjing Lu 1 Ruiqi Baiyun 1 Xiaoya Zhang 1 Yueying Lv 1 Hao Wu 1 Zhigang Zhang 3 4
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Harbin, 150030, China.
  • 2 Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 600 Changjiang Road, Harbin, 150030, China.
  • 3 College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Road, Harbin, 150030, China. zhangzhigang@neau.edu.cn.
  • 4 Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 600 Changjiang Road, Harbin, 150030, China. zhangzhigang@neau.edu.cn.
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.

Keywords

A2B adenosine receptor; Adenosine; Fibroblast-to-myofibroblast transition; Follistatin-like 1; High-performance liquid chromatography; Lung fibrosis; Multi-walled carbon nanotubes; Transforming growth factor-β1.

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