COVID-19 SPIKE Protein Directly Alters Pulmonary Fibroblast Mediated Remodeling of the Extracellular Matrix
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Date
2024-05
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The Ohio State University
Abstract
The Angiotensin-Converting Enzyme 2(ACE2) is the enzyme that the SARS-CoV-2 virus binds to causing mild to moderate respiratory effects also known as Coronavirus disease (COVID-19). In some patients COVID-19 can cause severe illness that can even result in death [1]. A higher level of expression of ACE2 has been linked to a greater chance of infection. The role of ACE2 in COVID-19 development has been primarily focused on epithelial cells, but fibroblasts which are involved in the development and remodeling of the extracellular matrix(ECM) could also have an important role. Previous studies have demonstrated that fibroblasts also contain a high level of ACE2 expression [3]. However, there is still a lot that is unknown about the mechanistic effects of higher ACE2 expression in fibroblasts and how that affects how COVID-19 manifests in the body. Specifically, although fibroblasts are the main cell responsible for the development of pulmonary fibrosis, a complication of COVID-19, it is not known how ACE2 expression or SARS-CoV-2 binding alters fibrotic remodeling of the ECM. Therefore, this study aims to investigate the functional significance of ACE2 in fibroblasts and COVID-19 pathogenesis. This will be accomplished by measuring the levels of ECM remodeling in normal and idiopathic pulmonary fibrosis(IPF) fibroblasts in the presence of COVID-19 spike protein, bacterial infection, and Rho-kinase inhibitor. This remodeling will be captured through confocal microscopy and analyzed through finite element analysis. A better understanding of fibroblasts’ contribution to COVID-19 is needed to develop better therapeutics for targeting this disease.
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Keywords
COVID-19, Pulmonary Fibrosis, Fibroblasts, Collagen, Spike, Finite Element Modeling