ArticleAmerican journal of physiology. Lung cellular and molecular physiology2023
The SARS-CoV-2 spike S1 protein induces global proteomic changes in ATII-like rat L2 cells that are attenuated by hyaluronan.
Article in American journal of physiology. Lung cellular and molecular physiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 6 citations in OpenAlex.
- The cell with many faces: lung macrophage plasticity and function in response to environmental and pathogenic insults.Physiological reviews · 2026Review
- Hyaluronan Ameliorates Viral Pneumonia in Mice and Humans by Inhibiting Transcription Factor E2F1.American journal of respiratory cell and molecular biology · 2026Article
- 14-3-3θ phosphorylation at S232 reduces its interactome and regulates axonal trafficking.Disease models & mechanisms · 2025Article
- Oxidative damage to lung mitochondrial DNA is a key contributor to the development of chemical lung injury.Redox biology · 2025Article
- Longitudinal Assessment of Nasopharyngeal Biomarkers Post-COVID-19: Unveiling Persistent Markers and Severity Correlations.Journal of proteome research · 2024Article
- Hemopexin reverses activation of lung eIF2α and decreases mitochondrial injury in chlorine-exposed mice.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Bioinformatics and system biology approach to identify the influences among COVID-19, influenza, and HIV on the regulation of gene expression.Frontiers in immunology · 2024Article
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8 authors at 2 institutions in 1 country.
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Abstract
The COVID-19 pandemic continues to impose a major impact on global health and economy since its identification in early 2020, causing significant morbidity and mortality worldwide. Caused by the SARS-CoV-2 virus, along with a growing number of variants, COVID-19 has led to 651,918,402 confirmed cases and 6,656,601 deaths worldwide (as of December 27, 2022; https://covid19.who.int/). Despite advances in our understanding of COVID-19 pathogenesis, the precise mechanism by which SARS-CoV2 causes epithelial injury is incompletely understood. In this current study, robust application of global-discovery proteomics identified highly significant induced changes by the Spike S1 protein of SARS-CoV-2 in the proteome of alveolar type II (ATII)-like rat L2 cells that lack ACE2 receptors. Systems biology analysis revealed that the S1-induced proteomics changes were associated with three significant network hubs: E2F1, CREB1/RelA, and ROCK2/RhoA. We also found that pretreatment of L2 cells with high molecular weight hyaluronan (HMW-HA) greatly attenuated the S1 effects on the proteome. Western blotting analysis and cell cycle measurements confirmed the S1 upregulation of E2F1 and ROCK2/RhoA in L2 cells and the protective effects of HMW-HA. Taken as a whole, our studies revealed profound and novel biological changes that contribute to our current understanding of both S1 and hyaluronan biology. These data show that the S1 protein may contribute to epithelial injury induced by SARS-CoV-2. In addition, our work supports the potential benefit of HMW-HA in ameliorating SARS CoV-2-induced cell injury.
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