High salt diet (HSD) is a hallmark of blood pressure elevations, weight gain and diabetes onset in the metabolic syndrome. In kidney, compensatory mechanisms are activated to balance salt turnover and maintain homeostasis. Data on the long-term effects of HSD with respect to tubular cell functions and kidney architecture that exclude confounding indirect blood pressure effects are scarce. Additionally we focus on cold shock Y-box binding protein-1 as a tubular cell protective factor. A HSD model (4% NaCl in chow; 1% NaCl in water) was compared to normal salt diet (NSD, standard chow) over 16 months using wild type mice and an inducible conditional whole body knockout for cold shock Y-box binding protein-1 (BL6J/N, Ybx1). HSD induced no difference in blood pressure over 16 months, comparing NSD/HSD and Ybx1 wild type/knockout. Nevertheless, marked phenotypic changes were detected. Glucosuria and subnephrotic albuminuria ensued in wild type animals under HSD, which subsided in Ybx1-deficient animals. At the same time megalin receptors were upregulated. The sodium-glucose cotransporter-2 (SGLT2) was completely downregulated in wild type HSD animals that developed glucosuria. In Ybx1 knockouts, expression of AQP1 and SGLT2 was maintained under HSD; proximal tubular widening and glomerular tubularization developed. Concurrently, amino aciduria of neutral and hydrophobic amino acids was seen. In vitro translation confirmed that YB-1 translationally represses Sglt2 transcripts. Our data reveal profound effects of HSD primarily within glomeruli and proximal tubular segments. YB-1 is regulated by HSD and orchestrates HSD-dependent changes; notably, sets reabsorption thresholds for amino acids, proteins and glucose.

中文翻译：

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高盐饮食诱导的近端肾小管表型变化和钠-葡萄糖协同转运蛋白-2 表达由冷休克 Y-box 结合蛋白-1 协调

高盐饮食 (HSD) 是代谢综合征中血压升高、体重增加和糖尿病发作的标志。在肾脏中，代偿机制被激活以平衡盐分转换和维持体内平衡。关于 HSD 对肾小管细胞功能和肾脏结构的长期影响（排除混杂的间接血压影响）的数据很少。此外，我们专注于冷休克 Y-box 结合蛋白-1 作为管状细胞保护因子。HSD 模型（食物中 4% NaCl；水中 1% NaCl）与正常盐饮食（NSD，标准食物）在 16 个月内使用野生型小鼠和冷休克 Y 盒结合蛋白的诱导性条件全身敲除进行比较-1（BL6J /N，Ybx1）。HSD 在 16 个月内没有引起血压差异，比较 NSD/HSD 和Ybx1野生型/敲除。然而，检测到显着的表型变化。糖尿和亚肾病蛋白尿在 HSD 下发生在野生型动物中，而在Ybx1 缺陷型动物中消退。同时，巨蛋白受体被上调。钠-葡萄糖协同转运蛋白-2 (SGLT2) 在发生糖尿的野生型 HSD 动物中完全下调。在Ybx1敲除中，AQP1 和 SGLT2 的表达在 HSD 下维持；近端肾小管增宽和肾小球肾小管化发展。同时，观察到中性和疏水性氨基酸的氨基酸尿。体外翻译证实 YB-1 在翻译上抑制Sglt2成绩单。我们的数据揭示了 HSD 主要在肾小球和近端肾小管段中的深远影响。YB-1 受 HSD 调控并协调 HSD 相关的变化；值得注意的是，设置了氨基酸、蛋白质和葡萄糖的重吸收阈值。