Increased expression of SCARF genes favoring SARS-CoV-2 infection in key target organs in chronic kidney disease (CKD).
Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 primarily causes lung damage, but can injure other organs and systems such as the kidneys or the gastrointestinal, cardiovascular, or nervous systems. Chronic kidney disease (CKD), especially diabetic disease, is the pathology that most increases the risk of death from COVID-19. However, the underlying cellular and molecular mechanisms are not clear. CKD, and especially renal failure, is a risk factor for infection, death from infection, and impaired response to vaccines. Therefore, the increased risk of severe COVID-19 may be due to a nonspecific alteration of antiviral responses in patients with CKD.
The uremic toxins that accumulate in CKD, and the consequent disruption of homeostasis, have a multisystemic impact, including differential expression of multiple genes in various organs. This may include dysregulation of the expression of SCARF genes, which are SARS-CoV-2 and coronavirus-associated receptors and factors whose function is to regulate cellular entry and/or replication of coronaviruses. The aim of this study was to analyze possible alterations in the expression of genes encoding SCARFs in COVID-19 target organs in mice with CKD, which may increase the risk of SARS-CoV-2 infection and/or its severity.
The role of Ly6e in this study
Ly6e is a SCARF gene that encodes for lymphocyte antigen 6 (LY6E) family member 6, a glycosylphosphatidylinositol (GPI)-anchored cell surface protein that modulates T cell activation and proliferation and has an antiviral immune effect controlling coronavirus infection. LY6E interferes with spike protein-mediated membrane fusion, protecting primary B cells against coronavirus infection and severe viral disease.
In this study, the expression of Ly6e was analyzed in mice induced with CKD to observe possible related alterations. This gene showed a lower expression than expected in one of the CKD target tissues, specifically in the aorta. This lower expression could be related to an increased sensitivity of the organism to SARS-CoV-2 infection, since this gene is known to protect against such infection. Because of this, the Ly6e gene was chosen to validate the impact of changes in gene expression on protein levels. After this analysis, a lower expression of both Ly6e mRNA and LY6E protein was observed in aorta of CKD mice.
A polyclonal antibody for Ly6e detection
The decrease in Ly6e expression in the aorta was confirmed by immunohistochemical techniques. For this purpose, the polyclonal anti-Ly6e antibody from Abyntek Research Reagents was used. This made it possible to relate the lower expression of the gene with a possible greater sensitivity of the mice to SARS-CoV-2 infection, as well as with a possible increase in the severity of COVID-19 in target organs, due to the fact that differential expression of the gene could favor the entry of the virus into the cells and/or their proliferation.
Abyntek Research Reagents is a product line of Abyntek Biopharma. With over 15 years of experience, Abyntek Biopharma has supported many research studies, helping to choose the most suitable biological reagents for biomarker analysis. In addition to offering its knowledge and expertise, Abyntek provides a diverse selection of high-quality products designed to meet the needs of researchers in this field.
Conclusion
This study demonstrates that chronic kidney disease (CKD), most commonly caused by diabetes, is associated with differential expression of multiple SCARF genes in COVID-19 target organs, some of which may sensitize to SARS-CoV-2 infection. Specifically, decreased expression of Ly6e may contribute to increased severity of COVID-19 in target organs in the context of CKD. This information may enable the development of therapeutic strategies aimed at decreasing the severity of future coronavirus pandemics in patients with this pathology.
This article was published in Clinical Kidney Journal on September 5, 2023.
