Exploration and verification of COVID-19-related hub genes in liver physiological and pathological regeneration

Abstract

Objectives An acute injury is often accompanied by tissue regeneration. In this process, epithelial cells show a tendency of cell proliferation under the induction of injury stress, inflammatory factors, and other factors, accompanied by a temporary decline of cellular function. Regulating this regenerative process and avoiding chronic injury is a concern of regenerative medicine. The severe coronavirus disease 2019 (COVID-19) has posed a significant threat to people’s health caused by the coronavirus. Acute liver failure (ALF) is a clinical syndrome resulting from rapid liver dysfunction with a fatal outcome. We hope to analyze the two diseases together to find a way for acute failure treatment.Methods COVID-19 dataset (GSE180226) and ALF dataset (GSE38941) were downloaded from the Gene Expression Omnibus (GEO) database, and the “Deseq2” package and “limma” package were used to identify differentially expressed genes (DEGs). Common DEGs were used for hub genes exploration, Protein-Protein Interaction (PPI) network construction, Gene Ontology (GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) was used to verify the role of hub genes in liver regeneration during in vitro expansion of liver cells and a CCl4-induced ALF mice model.Results: The common gene analysis of the COVID-19 and ALF databases revealed 15 hub genes from 418 common DEGs. These hub genes, including CDC20, were related to cell proliferation and mitosis regulation, reflecting the consistent tissue regeneration change after the injury. Furthermore, hub genes were verified in vitro expansion of liver cells and in vivo ALF model. On this basis, the potential therapeutic small molecule of ALF was found by targeting the hub gene CDC20.Conclusion We have identified hub genes for epithelial cell regeneration under acute injury conditions and explored a new small molecule Apcin for liver function maintenance and ALF treatment. These findings may provide new approaches and ideas for treating COVID-19 patients with ALF.

Understanding the SARS-CoV-2-Human Liver Interactome Using a Comprehensive Analysis of the Individual Virus-Host Interactions.

“…It also collects all the experimentally proven data on the interactions between the 31 SARS-CoV-2 proteins and the human proteome. The quantitative SAINT analysis [51] was used to identify SARS-CoV-2 viral-host proximity interactions in human or model system cells [11][12][13][14][15][16][17] and those with a Bayesian FDR =< 0.01 were high confidence. Scores are the sum of peptide counts from four mass spec runs with a higher score indicating a higher degree of connectivity between proteins.…”

“…As mentioned in the Introduction, we carefully selected 11 projects [13][14][15][16][17][18][19][20][21][22][23] out of the 18 projects identified in the scientific literature between 2021 and 2023. These papers deal with the characterization of hepatic metabolic processes that are viral targets in patients affected by COVID-19.…”

“…Through these genes, we can describe possible functions making metabolic hypotheses, aided by GO and KEGG analyses. Many researchers focused on the impact of the disease on evaluating the regeneration of liver epithelial cells [9,10], to create a model of acute liver failure and identify the possible therapeutic effects of inhibitors of some high ranked genes, such as hub genes [11]. Knowledge of hub genes, therefore, represents an indispensable crucial point for characterizing the molecular aspects of a disease, such as cellular stress due to COVID-19 but also for the design of specific drugs.…”

“…Some of our searches on PubMed performed using terms such as "COVID-19 AND liver hub genes" or similar terms, extracted eighteen studies, of which we selected eleven (2021-2023) [13][14][15][16][17][18][19][20][21][22][23] because they reported hub genes linked to COVID-19 (see also in the Results). These studies aim to determine regulatory processes from datasets based on microarray or transcriptome sequencing technology.…”

Understanding the SARS-CoV-2–Human Liver Interactome Using a Comprehensive Analysis of the Individual Virus–Host Interactions

“…Computational approaches, such as gene expression analysis, have emerged as valuable tools in understanding COVID-19 pathogenesis and its effects on liver metabolism [9,10]. By evaluating changes in gene expression, researchers have identified hub genes associated with COVID-19 [11], offering insights into disease progression and potential therapeutic tar-gets. These hub genes play crucial roles in coordinating metabolic processes, although there is disagreement in identifying, characterizing, and classifying these types of nodes [12].…”