2. Academic Validation
  3. SARS-COV-2 spike protein promotes RPE cell senescence via the ROS/P53/P21 pathway

SARS-COV-2 spike protein promotes RPE cell senescence via the ROS/P53/P21 pathway

  • Biogerontology. 2023 Feb 4;1-15. doi: 10.1007/s10522-023-10019-0.
Yuhang Zhang # 1,  Xuyan Peng # 1,  Mengjiao Xue # 1,  Jingjing Liu 1,  Guohui Shang 2,  Mingjun Jiang 1,  Dandan Chen 1,  Baixue Liu 1,  Yuxuan Wang 1,  Xiaolin Jia 1,  Jianqing Xu 3,  Fengyan Zhang 4 5,  Yanzhong Hu 6 7 8 9
Affiliations

Affiliations

  • 1 The Laboratory of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 2 Department of Medical Genetics and Cell Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
  • 3 Chongqing Institutes for Life Science Innovation; Clinical Center for Bio-Therapy, Zhongshan Hospital & Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, People's Republic of China.
  • 4 The Laboratory of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Zhangfengyanx@aliyun.com.
  • 5 The Division of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, No.1 Long-Hu-Zhong Huan Road, Zhengzhou, China. Zhangfengyanx@aliyun.com.
  • 6 The Laboratory of Ophthalmology and Vision Science, Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. hyz@henu.edu.cn.
  • 7 Joint National Laboratory for Antibody Drug Engineering, The First Affiliated Hospital of Henan University, Kaifeng, China. hyz@henu.edu.cn.
  • 8 Kaifeng Key Lab for Cataract and Myopia, Institute of Eye Disease, Kaifeng Central Hospital, Kaifeng, China. hyz@henu.edu.cn.
  • 9 Department of Cell Biology and Genetics, School of Medicine, Henan University, Jin-Ming Road, Kaifeng, 475014, China. hyz@henu.edu.cn.
  • # Contributed equally.
PMID: 36738354 DOI: 10.1007/s10522-023-10019-0
Abstract

SARS-Cov-2 Infection, which has caused the COVID-19 global pandemic, triggers cellular senescence. In this study, we investigate the role of the SARS-COV-2 spike protein (S-protein) in regulating the senescence of RPE cells. The results showed that administration or overexpression of S-protein in ARPE-19 decreased cell proliferation with cell cycle arrest at the G1 phase. S-protein increased SA-β-Gal positive ARPE-19 cells with high expression of P53 and P21, senescence-associated inflammatory factors (e.g., IL-1β, IL-6, IL-8, ICAM, and VEGF), and ROS. Elimination of ROS by N-acetyl cysteine (NAC) or knocking down p21 by siRNA diminished S-protein-induced ARPE cell senescence. Both administrated and overexpressed S-protein colocalize with the ER and upregulate ER-stress-associated BIP, CHOP, ATF3, and ATF6 expression. S-protein induced P65 protein nuclear translocation. Inhibition of NF-κB by bay-11-7082 reduced S-protein-mediated expression of senescence-associated factors. Moreover, the intravitreal injection of S-protein upregulates senescence-associated inflammatory factors in the zebrafish retina. In conclusions, the S-protein of SARS-Cov-2 induces cellular senescence of ARPE-19 cells in vitro and the expression of senescence-associated cytokines in zebrafish retina in vivo likely by activating ER stress, ROS, and NF-κB. These results may uncover a potential association between SARS-cov-2 Infection and development of AMD.

Keywords

RPE; SARS-Cov-2; Senescence; Spike protein; Zebrafish.

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