Abstract
Alveolar epithelial cells play an essential role in the initiation and progression of pulmonary fibrosis, and the occurrence of epithelial–mesenchymal transition (EMT) may be the early events of pulmonary fibrosis. Recent studies have shown chemokines are involved in the complex process of EMT, and CXC chemokine ligand 16 (CXCL16) is also associated with many fibrosis-related diseases. However, whether CXCL16 is dysregulated in alveolar epithelial cells and the role of CXCL16 in modulating EMT in pulmonary fibrosis has not been reported. In this study, we found that CXCL16 and its receptor C-X-C motif chemokine receptor 6 (CXCR6) were upregulated in bleomycin induced EMT in human alveolar type II-like epithelial A549 cells. Synergistic effect of CXCL16 and bleomycin in promoting EMT occurrence, extracellular matrix (ECM) excretion, as well as the pro-inflammatory and pro-fibrotic cytokines productions in A549 cells were observed, and those biological functions were impaired by CXCL16 siRNA. We further confirmed that CXCL16 regulated EMT in A549 cells via the TGF-β1/Smad3 pathways. These results indicated that CXCL16 could promote pulmonary fibrosis by promoting the process of EMT via the TGF-β1/Smad3 signaling pathway.
Highlights
Pulmonary fibrosis is a progressive and destructive lung disease with various causes, which seriously endangers patients’ health and life
CXC chemokine ligand 16 (CXCL16) and its receptor C-X-C motif chemokine receptor 6 (CXCR6) were upregulated in BLM‐induced epithelial–mesenchymal transition (EMT) in human A549 cells we detected the expression of CXCL16 and its receptor CXCR6 in BLM-induced EMT in A549 cells, by RT-PCR, western blot and immunofluorescence
We found that mRNA levels of CXCL16 and CXCR6 were markedly increased in A549 cells when treated with BLM, with similar results obtained in western blot and immunofluorescence (Fig. 2)
Summary
Pulmonary fibrosis is a progressive and destructive lung disease with various causes, which seriously endangers patients’ health and life. It is well-recognized that "pulmonary fibrosis" covers a broad range of lung diseases, including most topically the idiopathic pulmonary fibrosis (IPF), and connective tissue disease-associated interstitial lung disease (CTD-ILD) [1]. The pathogenesis and pathological process of pulmonary fibrosis is always divided into four parts: injury of the lung tissue with various causes, release of diverse proinflammatory and pro-fibrotic mediators, destruction of the tissue structures and the subsequent tissue repairs. Repeated and abnormal repair of the lung tissue results in the disorder of the internal environment and excessive deposition of extracellular matrix (ECM), and leads to the occurrence of pulmonary fibrosis [5]. Some studies have shown that alveolar macrophages, alveolar epithelial cells and pulmonary interstitial cells all participate in the development of pulmonary fibrosis by secreting inflammatory cytokines and mediators, directly
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