CD147 contributes to SARS-CoV-2-induced pulmonary fibrosis

被引：42

作者：

Wu, Jiao ^{[1
,2
]}

Chen, Liang ^{[3
]}

Qin, Chuan ^{[4
]}

Huo, Fei ^{[1
,2
]}

Liang, Xue ^{[1
,2
]}

Yang, Xu ^{[1
,2
]}

Zhang, Kui ^{[1
,2
]}

Lin, Peng ^{[1
,2
]}

Liu, Jiangning ^{[4
]}

Feng, Zhuan ^{[1
,2
]}

Zhou, Jiansheng ^{[1
,2
]}

Pei, Zhuo ^{[1
,2
]}

Wang, Yatao ^{[1
,2
]}

Sun, Xiu-Xuan ^{[1
,2
]}

Wang, Ke ^{[1
,2
]}

Geng, Jiejie ^{[1
,2
]}

Zheng, Zhaohui ^{[1
,2
]}

Fu, Xianghui ^{[1
,2
]}

Liu, Man ^{[1
,2
]}

Wang, Qingyi ^{[1
,2
]}

Zhang, Zheng ^{[1
,2
]}

Bian, Huijie ^{[1
,2
]}

Zhu, Ping ^{[1
,2
]}

Chen, Zhi-Nan ^{[1
,2
]}

机构：

[1] Fourth Mil Med Univ, Xijing Hosp, Natl Translat Sci Ctr Mol Med, Dept Cell Biol, Xian 710032, Peoples R China

[2] Fourth Mil Med Univ, Xijing Hosp, Dept Clin Immunol, Xian 710032, Peoples R China

[3] Shanghai Univ, Shanghai Engn Res Ctr Organ Repair, Sch Med, Shanghai 200444, Peoples R China

[4] Chinese Acad Med Sci, Inst Lab Anim Sci, Beijing 100071, Peoples R China

来源：

SIGNAL TRANSDUCTION AND TARGETED THERAPY | 2022年 / 7卷 / 01期

基金：

中国国家自然科学基金;

关键词：

CORONAVIRUS DISEASE 2019; TGF-BETA; COVID-19; PROMOTES; MATRIX-METALLOPROTEINASE-9; DIFFERENTIATION; INFLAMMATION; ACTIVATION; ROLES; CELLS;

D O I：

10.1038/s41392-022-01230-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：13

共 58 条

[1] Comparison of pirfenidone and corticosteroid treatments at the COVID-19 pneumonia with the guide of artificial intelligence supported thoracic computed tomography [J].