Ginsenoside Re Inhibits Pulmonary Fibrosis by Regulating <scp>CX3CL1</scp> / <scp>CX3CR1</scp> Axis

Pulmonary fibrosis is a chronic and irreversible pulmonary disease. At present, there are few drugs to treat pulmonary fibrosis, and effective targets are unknown. This study was aimed at exploring the mechanism of the anti-fibrosis effect of ginsenoside Re (Re). In vivo experiments determined the inhibitory effect of Re on bleomycin (BLM)-induced pulmonary fibrosis and explored whether it was related to the regulation of chemokine CX3C ligand 1 (CX3CL1)/chemokine CX3C receptor 1 (CX3CR1) axis. In vitro experiments, lentivirus transfection was employed to knock down CX3CL1 to further explore the role of the CX3CL1/CX3CR1 axis in the mode of action of Re in inhibiting pulmonary fibrosis. The pathological examination of mice lung tissues showed that Re attenuated BLM-induced pulmonary fibrosis in C57 BL/6J mice. The inhibitory effect of Re on pulmonary fibrosis was more potent in the wild-type mice than that in the CX3CL1^-/- mice. Transwell, Western Blot, and RT-qPCR results showed that Re could inhibit TGF-β1-induced epithelial-mesenchymal transition (EMT). In addition, the results showed that epithelial cells inhibited the anti-pulmonary fibrosis effect of Re after CX3CL1 knockdown. The anti-fibrosis effect of Re is related to the regulation of CX3CL1/CX3CR1, and the decreased CX3CL1 gene expression can inhibit the anti-fibrosis effect of Re.