| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Signal Transduction and Targeted Therapy, Vol 7, Iss 1, Pp 1-13 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2059-3635 |
| DOI: |
10.1038/s41392-022-01230-5 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
Full text from SpringerLink