CD147 contributes to SARS-CoV-2-induced pulmonary fibrosis.
Signal Transduct Target Ther
; 7(1): 382, 2022 Nov 25.
Article
in English
| MEDLINE | ID: covidwho-2133303
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Pulmonary Fibrosis
/
COVID-19
Type of study:
Prognostic study
Topics:
Long Covid
/
Variants
Limits:
Animals
Language:
English
Journal:
Signal Transduct Target Ther
Year:
2022
Document Type:
Article
Affiliation country:
S41392-022-01230-5
Similar
MEDLINE
...
LILACS
LIS