Signal Transduction and Targeted Therapy (Nov 2022)

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,
  • Xiu-Xuan Sun,
  • Ke Wang,
  • Jiejie Geng,
  • Zhaohui Zheng,
  • Xianghui Fu,
  • Man Liu,
  • Qingyi Wang,
  • Zheng Zhang,
  • Huijie Bian,
  • Ping Zhu,
  • Zhi-Nan Chen

DOI
https://doi.org/10.1038/s41392-022-01230-5
Journal volume & issue
Vol. 7, no. 1
pp. 1 – 13

Abstract

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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.