Oncotarget

Research Papers:

Activation of cannabinoid receptor type 2 by JWH133 alleviates bleomycin-induced pulmonary fibrosis in mice

Qiang Fu, Yi Zheng _, Xin Dong, Li Wang and Chun Guo Jiang

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Oncotarget. 2017; 8:103486-103498. https://doi.org/10.18632/oncotarget.21975

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Abstract

Qiang Fu1, Yi Zheng1, Xin Dong1, Li Wang2 and Chun Guo Jiang3

1Department of Rheumatology and Immunology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

2Department of Radiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

3Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China

Correspondence to:

Yi Zheng, email: zzyy90fs@126.com

Keywords: cannabinoid receptor type 2, JWH133, pulmonary fibrosis, bleomycin, mice

Received: July 03, 2017     Accepted: September 23, 2017     Published: October 19, 2017

ABSTRACT

Activation of cannabinoid receptor type 2 has been shown to have anti-fibrosis function in skin and heart. However, whether activating cannabinoid receptor type 2 inhibits pulmonary fibrosis remains elusive. Lung fibroblasts and TGF-β1 are key players in the pathogenesis of pulmonary fibrosis. In this research, we aimed to investigate the role of cannabinoid receptor type 2 in pulmonary fibrosis in vitro and in vivo. In lung fibroblasts stimulated by TGF-β1, preincubated by cannabinoid receptor type 2 agonist JWH133 not only reduced the elevated levels of collagen I and α-SMA, but also inhibited fibroblasts’ proliferation and migration. The dosage of JWH133 had no clear cytotoxic activity, and all these JWH133 effects were partially abrogated by cannabinoid receptor type 2 antagonist SR144528. In bleomycin-induced mice pulmonary fibrosis model, CT images of the lung tissue revealed an extensive ground-glass opacity, reticular pattern and fibrosis stranding. Notably, JWH133 treatment controlled the ongoing fibrotic process (showed by decreased lung density and fibrosis score). Meanwhile, lung histological results revealed that JWH133 treatment suppressed both the inflammatory response and extracellular collagen deposition. SR144528 may increase the pulmonary fibrosis, but no statistically significant difference was proved. Importantly, JWH133 reduced serum profibrotic cytokines levels of TGF-β1 and inhibited TGF-β1/Smad2 pathway in vitro and in vivo. Our research indicated that activating cannabinoid receptor type 2 by a pharmacological method might be a potential strategy for pulmonary fibrosis.


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