CD147 contributes to SARS-CoV-2-induced pulmonary fibrosis
Jiao Wu, Liang Chen, Chuan Qin, Fei Huo, Xue Liang, Xu Yang, Kui Zhang, Peng Lin, Jiangning Liu, Zhuan Feng, Jiansheng Zhou, Zhuo Pei, Yatao Wang, Xiuxuan Sun, Ke Wang, Jiejie Geng, Zhaohui Zheng, Xianghui Fu, Man Liu, Qingyi Wang, Zheng Zhang, Huijie Bian, Ping Zhu, Zhi‐Nan Chen
Abstract
COVID-19 patients can develop clinical and histopathological features associated with fibrosis, but the pathogenesis of fibrosis remains poorly understood. CD147 has been identified as a universal receptor for SARS-CoV-2 and its variants, which could initiate COVID-19-related cytokine storm. Here, we systemically analyzed lung pathogenesis in SARS-CoV-2- and its delta variant-infected humanized CD147 transgenic mice. Histopathology and Transmission Electron Microscopy revealed inflammation, fibroblast expansion and pronounced fibrotic remodeling in SARS-CoV-2-infected lungs. Consistently, RNA-sequencing identified a set of fibrosis signature genes. Furthermore, we identified CD147 as a crucial regulator for fibroblast activation induced by SARS-CoV-2. We found conditional knockout of CD147 in fibroblast suppressed activation of fibroblasts, decreasing susceptibility to bleomycin-induced pulmonary fibrosis. Meplazumab, a CD147 antibody, was able to inhibit the accumulation of activated fibroblasts and the production of ECM proteins, thus alleviating the progression of pulmonary fibrosis caused by SARS-CoV-2. In conclusion, we demonstrated that CD147 contributed to SARS-CoV-2-triggered progressive pulmonary fibrosis and identified CD147 as a potential therapeutic target for treating patients with post-COVID-19 pulmonary fibrosis.