tetano
Editor, Senior Moderator
Clin Kidney J
. 2023 Sep 5;16(12):2672-2682.
doi: 10.1093/ckj/sfad220. eCollection 2023 Dec. Increased expression of SCARF genes favoring SARS-CoV-2 infection in key target organs in CKD
Sol Carriazo[SUP] 1 2 [/SUP], Marta Ribagorda[SUP] 1 2 [/SUP], Aranzazu Pintor-Chocano[SUP] 1 2 [/SUP], Maria Vanessa Perez-Gomez[SUP] 1 2 3 [/SUP], Alberto Ortiz[SUP] 1 2 3 [/SUP], Maria Dolores Sanchez-Niño[SUP] 1 2 4 [/SUP]
Affiliations
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. Two genes reported to protect from SARS-CoV-2 were downregulated in at least two non-kidney target organs: Ifitm3 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: SARS-CoV-2; SCARF; chronic kidney disease; mortality; risk factor.
. 2023 Sep 5;16(12):2672-2682.
doi: 10.1093/ckj/sfad220. eCollection 2023 Dec. Increased expression of SCARF genes favoring SARS-CoV-2 infection in key target organs in CKD
Sol Carriazo[SUP] 1 2 [/SUP], Marta Ribagorda[SUP] 1 2 [/SUP], Aranzazu Pintor-Chocano[SUP] 1 2 [/SUP], Maria Vanessa Perez-Gomez[SUP] 1 2 3 [/SUP], Alberto Ortiz[SUP] 1 2 3 [/SUP], Maria Dolores Sanchez-Niño[SUP] 1 2 4 [/SUP]
Affiliations
- PMID: 38046008
- PMCID: PMC10689187
- DOI: 10.1093/ckj/sfad220
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. Two genes reported to protect from SARS-CoV-2 were downregulated in at least two non-kidney target organs: Ifitm3 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: SARS-CoV-2; SCARF; chronic kidney disease; mortality; risk factor.