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| Status |
Public on Aug 22, 2020 |
| Title |
Urinary phosphate-containing nanoparticle contributes to inflammation and kidney injury in salt-sensitive hypertension |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
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| Summary |
Although disturbed phosphate metabolism frequently accompanies chronic kidney disease, it is unclear whether it contributes to the progression of renal dysfunction. Here, we show that urinary phosphate-containing nanoparticles promote kidney injury in salt-sensitive hypertension. Remarkably, four weeks of high salt loading resulted in a 2.5-fold increase in urinary phosphate excretion in Dahl salt-sensitive rats on a normal phosphorus diet. Inhibition of intestinal phosphate absorption using sucroferric oxyhydroxide (SF) in this model suppressed phosphaturia, attenuating glomerulosclerosis and tubulointerstitial injury without significantly affecting serum phosphate, blood pressure, or urinary sodium levels. In the kidney, macrophage infiltration and inflammatory cytokine induction were ameliorated by SF. Additionally, macrophage infiltration but not myofibril hypertrophy was alleviated in the heart. In vitro, phosphate loading to proximal tubule cells significantly increased inflammatory cytokine Ccl2, which was abolished by the removal of phosphate-containing nanoparticles but not by the knockdown of phosphate transporter Slc34a1. Finally, transcriptome analysis revealed a potential role of complement C1q in renal inflammation associated with disturbed phosphate metabolism. These data demonstrate that increased phosphaturia promotes inflammation and renal injury from an early stage of salt-sensitive hypertension, and suggest the need for interventions against subclinical phosphate accumulation to improve the prognosis of hypertensive kidney disease.
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| Overall design |
Global gene expression in the kidneys of Dahl-S rats receiving 2.5%SF was compared with that of Dahl-S rats
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| Contributor(s) |
Wang Q, Shibata S |
| Citation(s) |
33060834 |
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| Submission date |
Jan 10, 2020 |
| Last update date |
Oct 27, 2020 |
| Contact name |
Shigeru Shibata |
| E-mail(s) |
shigeru.shibata@med.teikyo-u.ac.jp
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| Organization name |
Teikyo University School of Medicine
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| Department |
Division of Nephrology, Department of Internal Medicine
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| Street address |
Kaga 2-11-1
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| City |
Itabashi |
| State/province |
Tokyo |
| ZIP/Postal code |
173-8605 |
| Country |
Japan |
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| Platforms (1) |
| GPL22388 |
[RTA-1_0] Affymetrix Rat Transcriptome Array 1.0 [transcript (gene) CSV version] |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA600507 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE143440_RAW.tar |
43.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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