Aihua Wu, Yahua Zhang, Fabian Bock, Juan Pablo Arroyo, Eric Delpire, Ming-Zhi Zhang, Raymond C Harris, Andrew S Terker
{"title":"巨噬细胞 SPAK 缺失限制了低钾诱导的肾脏炎症程序。","authors":"Aihua Wu, Yahua Zhang, Fabian Bock, Juan Pablo Arroyo, Eric Delpire, Ming-Zhi Zhang, Raymond C Harris, Andrew S Terker","doi":"10.1152/ajprenal.00175.2024","DOIUrl":null,"url":null,"abstract":"<p><p>Inadequate dietary potassium (K<sup>+</sup>) consumption is a significant contributor to poor cardiovascular outcomes. A diet with reduced K<sup>+</sup> content has been shown to cause salt-sensitive increases in blood pressure. More recently we have also shown that reductions in blood K<sup>+</sup> can cause direct kidney injury, independent of dietary sodium (Na<sup>+</sup>) content. Here we investigated the role of the kinase, SPAK, in this kidney injury response. We observed that global SPAK deletion protected the kidney from damaging effects of a diet high in Na<sup>+</sup> and low in K<sup>+</sup>. We hypothesized kidney macrophages were contributing to the injury response and that macrophage-expressed SPAK is essential in this process. We observed SPAK protein expression in isolated macrophages in vitro. Culture in K<sup>+</sup>-deficient medium increased SPAK phosphorylation and caused SPAK to localize to cytosolic puncta, reminiscent of WNK bodies identified along the distal nephron epithelium. WNK1 also adopted a punctate staining pattern under low K<sup>+</sup> conditions and SPAK phosphorylation was prevented by treatment with the WNK inhibitor, WNK463. Macrophage-specific SPAK deletion in vivo protected against the low K<sup>+</sup>-mediated renal inflammatory and fibrotic responses. Our results highlight an important role for macrophages, and macrophage-expressed SPAK, in the propagation of kidney damage that occurs in response to reduced dietary K<sup>+</sup> consumption.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Macrophage SPAK deletion limits a low potassium-induced kidney inflammatory program.\",\"authors\":\"Aihua Wu, Yahua Zhang, Fabian Bock, Juan Pablo Arroyo, Eric Delpire, Ming-Zhi Zhang, Raymond C Harris, Andrew S Terker\",\"doi\":\"10.1152/ajprenal.00175.2024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Inadequate dietary potassium (K<sup>+</sup>) consumption is a significant contributor to poor cardiovascular outcomes. A diet with reduced K<sup>+</sup> content has been shown to cause salt-sensitive increases in blood pressure. More recently we have also shown that reductions in blood K<sup>+</sup> can cause direct kidney injury, independent of dietary sodium (Na<sup>+</sup>) content. Here we investigated the role of the kinase, SPAK, in this kidney injury response. We observed that global SPAK deletion protected the kidney from damaging effects of a diet high in Na<sup>+</sup> and low in K<sup>+</sup>. We hypothesized kidney macrophages were contributing to the injury response and that macrophage-expressed SPAK is essential in this process. We observed SPAK protein expression in isolated macrophages in vitro. Culture in K<sup>+</sup>-deficient medium increased SPAK phosphorylation and caused SPAK to localize to cytosolic puncta, reminiscent of WNK bodies identified along the distal nephron epithelium. WNK1 also adopted a punctate staining pattern under low K<sup>+</sup> conditions and SPAK phosphorylation was prevented by treatment with the WNK inhibitor, WNK463. Macrophage-specific SPAK deletion in vivo protected against the low K<sup>+</sup>-mediated renal inflammatory and fibrotic responses. Our results highlight an important role for macrophages, and macrophage-expressed SPAK, in the propagation of kidney damage that occurs in response to reduced dietary K<sup>+</sup> consumption.</p>\",\"PeriodicalId\":93867,\"journal\":{\"name\":\"American journal of physiology. Renal physiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American journal of physiology. 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Macrophage SPAK deletion limits a low potassium-induced kidney inflammatory program.
Inadequate dietary potassium (K+) consumption is a significant contributor to poor cardiovascular outcomes. A diet with reduced K+ content has been shown to cause salt-sensitive increases in blood pressure. More recently we have also shown that reductions in blood K+ can cause direct kidney injury, independent of dietary sodium (Na+) content. Here we investigated the role of the kinase, SPAK, in this kidney injury response. We observed that global SPAK deletion protected the kidney from damaging effects of a diet high in Na+ and low in K+. We hypothesized kidney macrophages were contributing to the injury response and that macrophage-expressed SPAK is essential in this process. We observed SPAK protein expression in isolated macrophages in vitro. Culture in K+-deficient medium increased SPAK phosphorylation and caused SPAK to localize to cytosolic puncta, reminiscent of WNK bodies identified along the distal nephron epithelium. WNK1 also adopted a punctate staining pattern under low K+ conditions and SPAK phosphorylation was prevented by treatment with the WNK inhibitor, WNK463. Macrophage-specific SPAK deletion in vivo protected against the low K+-mediated renal inflammatory and fibrotic responses. Our results highlight an important role for macrophages, and macrophage-expressed SPAK, in the propagation of kidney damage that occurs in response to reduced dietary K+ consumption.