tetano
Editor, Senior Moderator
Sci Rep
. 2024 Oct 16;14(1):24313.
doi: 10.1038/s41598-024-75338-9. SARS-CoV-2 infection causes a decline in renal megalin expression and affects vitamin D metabolism in the kidney of K18-hACE2 mice
Yoshifumi Kurosaki[SUP] 1 2 [/SUP], Toshihide Matsumoto[SUP] 2 3 [/SUP], Takayuki Uematsu[SUP] 4 [/SUP], Fumitaka Kawakami[SUP] 2 5 [/SUP], Rei Kawashima[SUP] 2 6 [/SUP], Shun Tamaki[SUP] 2 6 [/SUP], Motoki Imai[SUP] 2 7 [/SUP], Takafumi Ichikawa[SUP] 2 6 [/SUP], Naohito Ishii[SUP] 1 2 [/SUP], Hidero Kitasato[SUP] 2 8 [/SUP], Hideaki Hanaki[SUP] 9 [/SUP], Makoto Kubo[SUP] 10 11 [/SUP]
Affiliations
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.
. 2024 Oct 16;14(1):24313.
doi: 10.1038/s41598-024-75338-9. SARS-CoV-2 infection causes a decline in renal megalin expression and affects vitamin D metabolism in the kidney of K18-hACE2 mice
Yoshifumi Kurosaki[SUP] 1 2 [/SUP], Toshihide Matsumoto[SUP] 2 3 [/SUP], Takayuki Uematsu[SUP] 4 [/SUP], Fumitaka Kawakami[SUP] 2 5 [/SUP], Rei Kawashima[SUP] 2 6 [/SUP], Shun Tamaki[SUP] 2 6 [/SUP], Motoki Imai[SUP] 2 7 [/SUP], Takafumi Ichikawa[SUP] 2 6 [/SUP], Naohito Ishii[SUP] 1 2 [/SUP], Hidero Kitasato[SUP] 2 8 [/SUP], Hideaki Hanaki[SUP] 9 [/SUP], Makoto Kubo[SUP] 10 11 [/SUP]
Affiliations
- PMID: 39414885
- DOI: 10.1038/s41598-024-75338-9
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.