Scientists have identified five hub genes that might be associated with severe coronavirus disease 2019 (COVID-19) outcomes in patients with diabetic kidney disease. The study is currently available on the bioRxiv* preprint server.
Study: Discovering hub genes involved in the pathophysiological impact of COVID-19 on diabetes kidney disease by differential gene expression and interactome analysis. Image Credit: 3DJustincase/Shutterstock
This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources
Hub genes are those genes that exhibit many interactions with other genes and, thus, play important roles in regulating vital biological processes.
Background
Diabetes is a chronic endocrine disease that increases the risk of severe COVID-19. Evidence indicates that hyperinflammation is the primary causative factor of immunological complications during the clinical course of COVID-19. However, it is still uncertain how diabetes may increase the disease risk.
Diabetic kidney disease, also known as diabetic nephropathy, is a chronic kidney complication caused by hyperglycemia. About 30-40% of diabetic patients live with this health condition, and about 50% eventually develop end-stage kidney disease that requires dialysis or kidney transplantation.
Recent evidence has highlighted that patients with both diabetic kidney disease and COVID-19 develop multiple pathophysiological mechanisms between the lung and kidney. Patients with end-stage kidney disease also exhibit a higher risk of COVID-19-related mortality.
In the current study, scientists have conducted transcriptomics and network analysis to identify critical genes shared by the pathways affected by COVID-19 and diabetic kidney disease.
Study design
The scientists conducted bioinformatics analysis of transcriptomic data obtained from patients with diabetic kidney disease to identify predictive hub genes associated with COVID-19-related diabetic kidney complications.
They characterized the genes that were differentially expressed in both disease conditions. Furthermore, they conducted a functional enrichment analysis of differentially expressed genes in the diabetic kidney disease dataset.
To identify the hub genes, they performed a protein-protein interaction network and topological analysis. Finally, they determined the co-expression modules of the identified hub genes and assessed their tissue-specific regulation.
Important observations
A total of 995 differentially expressed genes were characterized in the diabetic kidney disease dataset. Of these genes, 42 were connected to the COVID-19-related pathways and showed an upregulated expression profile.
A particular group of upregulated differentially expressed genes was connected to the complement and coagulation systems, which are known to associate with the pathophysiological mechanisms of COVID-19. As mentioned by the scientists, the interplay between complement- and coagulation-related biomolecules could significantly worsen COVID-19 outcomes in patients with diabetic kidney disease.
Another group of upregulated differentially expressed genes showed strong associations with pro-inflammatory, cell activation, oxidative stress, cell adhesion, and apoptosis pathways. In addition, some upregulated genes were found to associate with pathogen recognition receptor pathways, which are the vital components of the innate immune system to fight against invading pathogens.
Overall, these observations indicate that the overactivation of the innate immune system and inflammatory pathways due to aberrant gene expressions may act in a negative synergistic manner to cause the worst COVID-19 outcomes in patients with diabetic kidney disease.
Hub genes
The protein-protein network analysis identified a particular set of five hub genes, including STAT1, IRF7, ISG15, MX1, and OAS1. Besides being associated with COVID-19- and diabetic kidney disease-related biological and metabolic pathways, the hub genes showed strong connections with heart disease, impaired angiogenesis, and metabolic diseases.
The interactome analysis findings revealed that the hub genes are co-expressed with other genes involved in cardiovascular disease, virus immune response, and genetic regulation at the transcriptional and post-transcriptional levels.
Tissue-specific expression profile analysis of hub genes revealed that ISG15, STAT1, and MX1 have a consistently upregulated expression profile in the immune cells of COVID-19 patients. In addition, MX1 and OAS1 exhibited a lower expression profile in healthy kidney tissues.
As mentioned by the scientists, persistent activation of immune cells in chronic kidney disease together with higher expression of ISG15, STAT1, and MX1 can lead to higher production of pro-inflammatory cytokines and subsequent worsening of COVID-19 outcomes.
Study significance
The study identifies five hub genes that may play crucial roles in worsening COVID-19 outcomes in patients with diabetic kidney disease. These genes are associated with innate immune and inflammatory systems.
These genes can serve as potential prognostic or therapeutic targets to facilitate the development of novel drugs against COVID-19.
This news article was a review of a preliminary scientific report that had not undergone peer-review at the time of publication. Since its initial publication, the scientific report has now been peer reviewed and accepted for publication in a Scientific Journal. Links to the preliminary and peer-reviewed reports are available in the Sources section at the bottom of this article. View Sources
Article Revisions
- May 16 2023 - The preprint preliminary research paper that this article was based upon was accepted for publication in a peer-reviewed Scientific Journal. This article was edited accordingly to include a link to the final peer-reviewed paper, now shown in the sources section.
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