Urinary phosphate-containing nanoparticle contributes to inflammation and kidney injury in a salt-sensitive hypertension rat model.

Urinary phosphate-containing nanoparticle contributes to inflammation and kidney injury in a salt-sensitive hypertension rat model.
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尿液中含磷酸盐的纳米颗粒会导致盐敏感高血压大鼠模型的炎症和肾损伤

DOI:
10.1038/s42003-020-01298-1
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发表时间:
2020-10-15
影响因子:
5.9
通讯作者:
Shibata S
Shibata S
中科院分区:
生物学2区
文献类型:
--
作者:
Wang Q;Ishizawa K;Li J;Fujii W;Nemoto Y;Yamazaki O;Tamura Y;Miura Y;Nie X;Abe R;Segawa H;Kuro-O M;Shibata S

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尽管磷酸盐代谢紊乱经常伴随慢性肾脏病(CKD),但其在CKD进展中的因果作用仍不清楚。过量的盐是如何引起器官损伤的也没有完全了解。我们在这里表明,尿中含磷酸盐的纳米颗粒促进盐敏感性高血压的肾损伤。在Dahl盐敏感大鼠中,盐负荷导致尿磷酸盐排泄显著增加,而不改变血清磷酸盐水平。肠内磷酸盐结合剂氢氧化蔗糖铁减轻了该模型中的肾脏炎症和蛋白尿,沿着磷酸盐尿的抑制。使用培养的近端小管细胞,我们证实了直接致病的作用,含磷酸盐的纳米颗粒在肾小管。最后,转录组分析揭示了补体C1q在与磷酸盐代谢改变相关的肾脏炎症中的潜在作用。这些数据表明,增加磷酸盐排泄促进盐敏感性高血压的肾脏炎症,并表明磷酸盐代谢紊乱的高血压肾病和高盐诱导的肾损伤的病理生理学中的作用。
Although disturbed phosphate metabolism frequently accompanies chronic kidney disease (CKD), its causal role in CKD progression remains unclear. It is also not fully understood how excess salt induces organ damage. We here show that urinary phosphate-containing nanoparticles promote kidney injury in salt-sensitive hypertension. In Dahl salt-sensitive rats, salt loading resulted in a significant increase in urinary phosphate excretion without altering serum phosphate levels. An intestinal phosphate binder sucroferric oxyhydroxide attenuated renal inflammation and proteinuria in this model, along with the suppression of phosphaturia. Using cultured proximal tubule cells, we confirmed direct pathogenic roles of phosphate-containing nanoparticles in renal tubules. Finally, transcriptome analysis revealed a potential role of complement C1q in renal inflammation associated with altered phosphate metabolism. These data demonstrate that increased phosphate excretion promotes renal inflammation in salt-sensitive hypertension and suggest a role of disturbed phosphate metabolism in the pathophysiology of hypertensive kidney disease and high salt-induced kidney injury.
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