Mouse model establishment and therapeutic evaluation of radiation-induced pulmonary fibrosis
YANG Jiecheng
HOU Rong
YANG Liu
ZHANG Yang
WANG Ke
Abstract：Objective To investigate the inhibitory effect of meplazumab,a humanized antibody targeting CD147,on the progression of pulmonary fibrosis by constructing a human CD147(hCD147)mouse model of radiation-induced pulmonary fibrosis based on gene editing technology,thereby providing experimental evidence for the clinical treatment of radiation-induced lung injury.Methods A mouse model of radiation-induced pulmonary fibrosis was established by 60Co irradiation.Lung tissue samples from mice on the 10th day after irradiation and the non-irradiated group(day 0)were collected for transcriptome sequencing to clarify the characteristics of radiation-mediated pulmonary inflammatory injury.The hCD147 mouse model of radiation-induced pulmonary fibrosis was constructed and divided into two groups,and on the 2nd,4th and 6th days after irradiation,3 mg/kg of IgG(IgG group)and meplazumab(meplazumab group)were intraperitoneally injected,respectively.The therapeutic effect of the antibody was evaluated by body mass monitoring,histopathological staining,and Western blotting experiments.Results A mouse model of radiation-induced pulmonary fibrosis induced by 60Co irradiation was successfully established.On the 10th day post-irradiation,the mice exhibited a significant body mass decline and acute inflammatory injury in their lung tissues.Transcriptome sequencing revealed that the differentially expressed genes in lung tissues between unirradiated and irradiated mice on the 10th day after irradiation were closely associated with immune-inflammatory responses.Compared with day 0,the levels of TNF-α and IL-1β in the lung tissues of irradiated mice were significantly elevated on the 10th day.Masson staining results demonstrated that from the 30th to the 120th day post-irradiation,the lung tissues displayed progressive chronic fibrosis characteristics,accompanied by increased collagen fiber deposition.Additionally,the expression level of α-SMA in the lung tissues of irradiated mice on the 120th day was significantly higher than that on day 0.Furthermore,hCD147 mice were successfully constructed via gene editing technology and then subjected to 60Co irradiation.Compared with the IgG group,mice in the meplazumab group showed better body mass recovery,reduced pulmonary inflammatory injury and collagen fiber deposition,as well as lower α-SMA expression level.Conclusion This study successfully establishes a mouse model of radiation-induced pulmonary fibrosis via 60 Co irradiation.The lung tissues of the mice exhibit a pathological progression from acute inflammatory injury to chronic fibrosis.Meplazumab targeting CD 147 alleviates pulmonary inflammatory injury and inhibits the fibrotic process,thereby providing a potential therapeutic target for radiation-induced pulmonary fibrosis.
Keywords：human CD 147 mouseradiation-induced pulmonary fibrosisinflammatory injurymeplazumabimmune responsecollagen fiberefficacy evaluationtherapeutic target
Publication Date：2026-07-31
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：8( 1000-1007 )