Li Fei, Xu Xuefeng, Geng Jing, Wan Xuan, Dai Huaping
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.
Exp Ther Med. 2020 Mar;19(3):1844-1854. doi: 10.3892/etm.2020.8433. Epub 2020 Jan 8.
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 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.
C-X-C基序趋化因子受体4/C-X-C基序趋化因子配体12（CXCR4/CXCL12）轴与肺纤维化的发病机制有关。然而，其调控机制仍有待确定。当前研究表明，人肺成纤维细胞（HLFs）表现出高CXCL12表达，并且也表现出其相应受体CXCR4的高表达。已揭示外源性CXCL12可显著促进HLFs的迁移和增殖，并增强CXCR4表达。这些作用被证明可被CXCR4拮抗剂AMD3100抑制。博来霉素给药可上调肺和支气管肺泡灌洗液中CXCR4和CXCL12的表达，而AMD3100预处理可部分抑制这种上调。AMD3100还可降低博来霉素模型中的肺胶原含量。抑制CXCR4被表明可改善肺纤维化的肺顺应性和阻力。总之，本研究结果表明自分泌CXCR4/CXCL12轴是特发性肺纤维化发病机制的重要机制，并且可能作为可用于治疗肺部疾病的潜在治疗靶点。
