SARS-CoV-2 uptake and inflammatory response in senescent endothelial cells are regulated by the BSG/VEGFR2 pathway
Abstract
Aging is a risk factor for severe COVID-19, characterized by vascular endothelial dysfunction. Although possible susceptibility of vascular endothelial cells (ECs) to SARS-CoV-2 infection has been suggested, the details of entry into cells have not been clarified. Previously, we reported that in an aged mouse model of severe COVID-19, ECs show a massive viral uptake and inflammatory response. Here, we focused on the endocytic capacity of senescent ECs. We found that the senescent ECs showed high endocytic capacity and SARS-CoV-2 virus uptake. This triggers an nuclear factor-kappa B (NF-κB) pathway–mediated inflammatory response. Further, Basigin enhanced endocytosis in the senescent ECs by activating the intracellular vascular endothelial growth factor signaling. Thus, EC senescence is associated with enhanced SARS-CoV-2 endocytosis and subsequent vascular endothelial dysfunction. This could prove a potential target for treating severe COVID-19 in older adults.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (14)
Yuya Sakurai
Vascular Biology and Molecular Pathology, Faculty and Graduate School of Dental Medicine, Hokkaido University
Yoichiro Fujioka
Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University
Nako Maishi
Vascular Biology and Molecular Pathology, Faculty and Graduate School of Dental Medicine, Hokkaido University
Ryo Takeda
Department of Interdisciplinary Engineering Sciences, Interdisciplinary Graduate School of Engineering Sciences
Yusuke Ohba
Department of Cell Physiology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University
Michihito Sasaki
Takahito Teshirogi
Vascular Biology and Molecular Pathology, Faculty and Graduate School of Dental Medicine, Hokkaido University
Wataru Ito
Vascular Biology and Molecular Pathology, Faculty and Graduate School of Dental Medicine, Hokkaido University
Yasuhiro Hida
Department of Thoracic Surgery, Fujita Health University Bantane Hospital
Aya Matsuda
Vascular Biology and Molecular Pathology, Faculty and Graduate School of Dental Medicine, Hokkaido University
Kanta Kido
Department of Dental Anesthesiology, Faculty and Graduate School of Dental Medicine, Hokkaido University
Yasuko Orba
Hirofumi Sawa
Kyoko Hida
Vascular Biology and Molecular Pathology, Faculty and Graduate School of Dental Medicine, Hokkaido University