Expression profiles of respiratory V-ATPase and calprotectin in SARS-CoV-2 infection

Abstract Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a pandemic threat that has been declared a public health emergency of international concern, whereas the effects of cellular microenvironment in the pathogenesis of SARS-CoV...

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Main Authors: Yapeng Hou, Tingyu Wang, Yan Ding, Tong Yu, Yong Cui, Hongguang Nie
Format: Article
Language:English
Published: Nature Publishing Group 2022-08-01
Series:Cell Death Discovery
Online Access:https://doi.org/10.1038/s41420-022-01158-3
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author Yapeng Hou
Tingyu Wang
Yan Ding
Tong Yu
Yong Cui
Hongguang Nie
author_facet Yapeng Hou
Tingyu Wang
Yan Ding
Tong Yu
Yong Cui
Hongguang Nie
author_sort Yapeng Hou
collection DOAJ
description Abstract Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a pandemic threat that has been declared a public health emergency of international concern, whereas the effects of cellular microenvironment in the pathogenesis of SARS-CoV-2 are poorly understood. The detailed message of intracellular/lysosome pH was rarely concerned in SARS-CoV-2 infection, which was crucial for the cleavage of SARS-CoV-2 spike (S) protein. Calprotectin, an endogenous danger signal to activate inflammatory response, was vital for the proceeding of COVID-19. We found that the expressions of both vacuolar-ATPase (V-ATPase) and calprotectin (S100A8/S100A9) increased in SARS-CoV-2 infection, by analyzing single-cell RNA sequencing (bronchoalveolar lavage fluid), bulk-RNA sequencing (A549, lung tissue, NHBE), and proteomics (lung tissue), respectively. Furtherly, our wet experiments of flow cytometry and fluorescent assay identified that the intracellular and lysosome pH value was decreased after SARS-CoV-2 S plasmid transfection in A549 cells. Meanwhile, the enhancement of V-ATPase and calprotectin was verified by our real-time polymerase chain reaction and western blot experiment. Collectively, these data suggested that S protein increased V-ATPase in SARS-CoV-2 infection, which provided a microenvironment easier for the cleavage of S protein, and inflammatory cells were apt to be activated by the enhancement of calprotectin in respiratory epithelium. The comprehensive information on profiles of V-ATPase and calprotectin will make clearer about the involvement of cellular microenvironment in the pathogenesis of SARS-CoV-2, and provide a promising approach to combat COVID-19.
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spelling doaj.art-c54700a74803495abf9d1371d850f36a2022-12-22T01:37:17ZengNature Publishing GroupCell Death Discovery2058-77162022-08-01811710.1038/s41420-022-01158-3Expression profiles of respiratory V-ATPase and calprotectin in SARS-CoV-2 infectionYapeng Hou0Tingyu Wang1Yan Ding2Tong Yu3Yong Cui4Hongguang Nie5Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical UniversityDepartment of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical UniversityDepartment of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical UniversityDepartment of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical UniversityDepartment of Anesthesiology, the First Hospital of China Medical UniversityDepartment of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical UniversityAbstract Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a pandemic threat that has been declared a public health emergency of international concern, whereas the effects of cellular microenvironment in the pathogenesis of SARS-CoV-2 are poorly understood. The detailed message of intracellular/lysosome pH was rarely concerned in SARS-CoV-2 infection, which was crucial for the cleavage of SARS-CoV-2 spike (S) protein. Calprotectin, an endogenous danger signal to activate inflammatory response, was vital for the proceeding of COVID-19. We found that the expressions of both vacuolar-ATPase (V-ATPase) and calprotectin (S100A8/S100A9) increased in SARS-CoV-2 infection, by analyzing single-cell RNA sequencing (bronchoalveolar lavage fluid), bulk-RNA sequencing (A549, lung tissue, NHBE), and proteomics (lung tissue), respectively. Furtherly, our wet experiments of flow cytometry and fluorescent assay identified that the intracellular and lysosome pH value was decreased after SARS-CoV-2 S plasmid transfection in A549 cells. Meanwhile, the enhancement of V-ATPase and calprotectin was verified by our real-time polymerase chain reaction and western blot experiment. Collectively, these data suggested that S protein increased V-ATPase in SARS-CoV-2 infection, which provided a microenvironment easier for the cleavage of S protein, and inflammatory cells were apt to be activated by the enhancement of calprotectin in respiratory epithelium. The comprehensive information on profiles of V-ATPase and calprotectin will make clearer about the involvement of cellular microenvironment in the pathogenesis of SARS-CoV-2, and provide a promising approach to combat COVID-19.https://doi.org/10.1038/s41420-022-01158-3
spellingShingle Yapeng Hou
Tingyu Wang
Yan Ding
Tong Yu
Yong Cui
Hongguang Nie
Expression profiles of respiratory V-ATPase and calprotectin in SARS-CoV-2 infection
Cell Death Discovery
title Expression profiles of respiratory V-ATPase and calprotectin in SARS-CoV-2 infection
title_full Expression profiles of respiratory V-ATPase and calprotectin in SARS-CoV-2 infection
title_fullStr Expression profiles of respiratory V-ATPase and calprotectin in SARS-CoV-2 infection
title_full_unstemmed Expression profiles of respiratory V-ATPase and calprotectin in SARS-CoV-2 infection
title_short Expression profiles of respiratory V-ATPase and calprotectin in SARS-CoV-2 infection
title_sort expression profiles of respiratory v atpase and calprotectin in sars cov 2 infection
url https://doi.org/10.1038/s41420-022-01158-3
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