SARS-CoV-2 infection causes a decline in renal megalin expression and affects vitamin D metabolism in the kidney of K18-hACE2 mice.
Animals
Low Density Lipoprotein Receptor-Related Protein-2
/ metabolism
Mice
COVID-19
/ metabolism
Vitamin D
/ metabolism
Angiotensin-Converting Enzyme 2
/ metabolism
Humans
Kidney
/ metabolism
SARS-CoV-2
Receptors, Calcitriol
/ metabolism
Kidney Tubules, Proximal
/ metabolism
Acute Kidney Injury
/ metabolism
Male
Disease Models, Animal
Mice, Transgenic
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
16 10 2024
16 10 2024
Historique:
received:
25
01
2024
accepted:
04
10
2024
medline:
17
10
2024
pubmed:
17
10
2024
entrez:
16
10
2024
Statut:
epublish
Résumé
Patients with coronavirus disease 2019 (COVID-19) often experience acute kidney injury, linked to disease severity or mortality, along with renal tubular dysfunction and megalin loss in proximal tubules. Megalin plays a crucial role in kidney vitamin D metabolism. However, the impact of megalin loss on vitamin D metabolism during COVID-19 is unclear. This study investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection reduces megalin expression in proximal tubules and its subsequent effect on vitamin D metabolism in mice expressing human angiotensin converting enzyme 2 (K18-hACE2 mice). Histological and immunohistochemical staining analyses revealed glomerular and capillary congestion, and elevated renal neutrophil gelatinase-associated lipocalin levels, indicative of acute kidney injury in K18-hACE2 mice. In SARS-CoV-2-infected mice, immunohistochemical staining revealed suppressed megalin protein levels. Decreased vitamin D receptor (VDR) localization in the nucleus and increased mRNA expression of VDR, CYP27B1, and CYP24A1 were observed by quantitative PCR in SARS-CoV-2-infected mice. Serum vitamin D levels remained similar in infected and vehicle-treated mice, but an increase in tumor necrosis factor-alpha and a decrease in IL-4 mRNA expression were observed in the kidneys of the SARS-CoV-2 group. These findings suggest that megalin loss in SARS-CoV-2 infection may impact the local role of vitamin D in kidney immunomodulation, even when blood vitamin D levels remain unchanged.
Identifiants
pubmed: 39414885
doi: 10.1038/s41598-024-75338-9
pii: 10.1038/s41598-024-75338-9
doi:
Substances chimiques
Low Density Lipoprotein Receptor-Related Protein-2
0
Vitamin D
1406-16-2
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Receptors, Calcitriol
0
Lrp2 protein, mouse
0
ACE2 protein, human
EC 3.4.17.23
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
24313Subventions
Organisme : School of Allied Health Sciences, Kitasato University
ID : Grant-in-Aid for Research Project No. 2022-1020
Informations de copyright
© 2024. The Author(s).
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