The autocrine CXCR4/CXCL12 axis contributes to lung fibrosis through modulation of lung fibroblast activity

Li,Fei; Xu,Xuefeng; Geng,Jing; Wan,Xuan; Dai,Huaping

doi:10.3892/etm.2020.8433

The autocrine CXCR4/CXCL12 axis contributes to lung fibrosis through modulation of lung fibroblast activity

Authors:
- Fei Li
- Xuefeng Xu
- Jing Geng
- Xuan Wan
- Huaping Dai
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Affiliations: Department of Pulmonary and Critical Care Medicine, Beijing An‑Zhen Hospital, Capital Medical University, Beijing 100029, P.R. China, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China‑Japan Friendship Hospital, Capital Medical University, National Clinical Research Center for Respiratory Diseases, Beijing 100029, P.R. China, Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: January 8, 2020 https://doi.org/10.3892/etm.2020.8433
Pages: 1844-1854
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The C‑X‑C Motif Chemokine Receptor 4/C‑X‑C Motif Chemokine Ligand 12 (CXCR4/CXCL12) axis has been implicated in the pathogenesis of pulmonary fibrosis. However, the mechanisms governing this remain to be determined. The current study demonstrated that human lung fibroblasts (HLFs) exhibit high CXCL12 expression and also exhibit high expression of its corresponding receptor CXCR4. Exogenous CXCL12 was revealed to significantly promote the migration and proliferation of HLFs, and potentiate CXCR4 expression. These effects were demonstrated to be inhibited by AMD3100, which is an antagonist of CXCR4. Lung and bronchoalveolar lavage fluid CXCR4 and CXCL12 expression was upregulated by in vivo bleomycin administration, which was partially inhibited by pre‑treatment with AMD3100. AMD3100 also reduced lung collagen content in the bleomycin model. Inhibiting CXCR4 was indicated to ameliorate the lung compliance and resistance of pulmonary fibrosis. In conclusion, the results of the present study suggested that autocrine CXCR4/CXCL12 axis is an important mechanism underlying the pathogenesis of idiopathic pulmonary fibrosis, and may serve as a potential therapeutic target that can be used in the treatment of pulmonary disease.

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