학술논문

Increased expression of SCARF genes favoring SARS-CoV-2 infection in key target organs in CKD
Document Type
Academic Journal
Source
Clinical Kidney Journal. December, 2023, Vol. 16 Issue 12, p2672, 11 p.
Subject
Spain
Language
English
ISSN
2048-8505
Abstract
Background. Chronic kidney disease (CKD), especially diabetic CKD, is the condition that most increases the risk of lethal coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the underlying molecular mechanisms are unclear. SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) regulate coronavirus cell entry and/or replication. We hypothesized that CKD may alter the expression of SCARF genes. Methods. A literature search identified 34 SCARF genes of which we selected 21 involved in interactions between SARS-CoV/SARS-CoV-2 and host cells, and assessed their mRNA expression in target tissues of COVID-19 (kidneys, lungs, aorta and heart) in mice with adenine-induced CKD. Results. Twenty genes were differentially expressed in at least one organ in mice with CKD. For 15 genes, the differential expression would be expected to favor SARS-CoV-2 infection and/or severity. Of these 15 genes, 13 were differentially expressed in the kidney and 8 were validated in human CKD kidney transcriptomics datasets, including those for the most common cause of CKD, diabetic nephropathy. Tw o genes reported to protect from SARS-CoV-2 were downregulated in at least two non-kidney target organs: Iftm3 encoding interferon-induced transmembrane protein 3 (IFITM3) in lung and Ly6e encoding lymphocyte antigen 6 family member 6 (LY6E) in aorta. Conclusion. CKD, including diabetic CKD, is associated with the differential expression of multiple SCARF genes in target organs of COVID-19, some of which may sensitize to SARS-CoV-2 infection. This information may facilitate developing therapeutic strategies aimed at decreasing COVID-19 severity in patients with CKD. Keywords: chronic kidney disease, mortality, risk factor, SARS-CoV-2, SCARF
INTRODUCTION Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). The SARS-CoV-2 pandemic has caused over 6.6 million deaths [1]. SARS-CoV-2 causes primarily pulmonary damage but can [...]