ArticleLaboratory investigation; a journal of technical methods and pathology2017
Sodium chloride promotes tissue inflammation via osmotic stimuli in subtotal-nephrectomized mice.
Article in Laboratory investigation; a journal of technical methods and pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Trial
- Multiple 24-Hour Urinary Sodium and Potassium Excretions and Type 2 Diabetes Incidence.Diabetes care · 2026Article
- Salt and chronic kidney disease.Nature reviews. Nephrology · 2026Review
- Distinct Tear Element Signatures in Primary Acquired Nasolacrimal Duct Obstruction Identified by Particle-Induced X-Ray Emission.Investigative ophthalmology & visual science · 2026Article
- Unraveling the pleiotropic effects of CCR2-dependent signal transduction in fibrosis development.Theranostics · 2026Review
- Blood pressure reduction and anti-inflammatory macrophage augmentation attenuate uterine immune dysregulation and inflammation in mice with salt-sensitive hypertension.Clinical science (London, England : 1979) · 2025Article
- Nonatherosclerotic Cardiovascular Disease in Chronic Kidney Disease.Cardiology clinics · 2025Review
- Hypertonic Saline Induces Host Protective Immune Responses againstJournal of microbiology and biotechnology · 2024Article
- Pathophysiological Mechanisms of Peritoneal Fibrosis and Peritoneal Membrane Dysfunction in Peritoneal Dialysis.International journal of molecular sciences · 2024Review
- Differential changes in end organ immune cells and inflammation in salt-sensitive hypertension: effects of lowering blood pressure.Clinical science (London, England : 1979) · 2024Article
- Common salt aggravated pathology of testosterone-induced benign prostatic hyperplasia in adult male Wistar rat.BMC urology · 2023Article
- High Salt Promotes Inflammatory and Fibrotic Response in Peritoneal Cells.International journal of molecular sciences · 2023Article
- Tissue Sodium Accumulation Induces Organ Inflammation and Injury in Chronic Kidney Disease.International journal of molecular sciences · 2023Review
- Association of early dysnatremia with mortality in the neonatal intensive care unit: results from the AWAKEN study.Journal of perinatology : official journal of the California Perinatal Association · 2022Article
- The modulatory effect of high salt on immune cells and related diseases.Cell proliferation · 2022Review
- Tissue Sodium Accumulation: Pathophysiology and Clinical Implications.Antioxidants (Basel, Switzerland) · 2022Review
- Role of Oxidative Stress in Vascular Low-Grade Inflammation Initiation Due to Acute Salt Loading in Young Healthy Individuals.Antioxidants (Basel, Switzerland) · 2022Article
- Volume-Independent Sodium Toxicity in Peritoneal Dialysis: New Insights from Bench to Bed.International journal of molecular sciences · 2021Review
- Thromboxane AClinical and experimental pharmacology & physiology · 2021Article
- The functional duality of SGK1 in the regulation of hyperglycemia.Endocrine connections · 2020Review
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic inflammation, which is often associated with high all-cause and cardiovascular mortality, is prevalent in patients with renal failure; however, the precise mechanisms remain unclear. High-salt intake was reported to induce lymphangiogenesis and autoimmune diseases via osmotic stimuli with accumulation of sodium or chloride. In addition, sodium was recently reported to be stored in the extremities of dialysis patients. We studied the effects and mechanisms of high salt loading on tissue and systemic inflammation in subtotal-nephrectomized mice (5/6Nx) and in cultured cells. Macrophage infiltration in the peritoneal wall (P<0.001), heart (P<0.05) and para-aortic tissues (P<0.001) was significantly higher in 5/6Nx with salt loading (5/6Nx/NaCl) than in 5/6Nx without salt loading (5/6Nx/Water); however, there were no significant differences in blood pressure and renal function between the groups. Tissue interleukin-6, monocyte chemotactic protein-1 (MCP-1), serum- and glucocorticoid-inducible kinase 1 (Sgk1) and tonicity-responsive enhancer binding protein (TonEBP) mRNA were significantly elevated in the peritoneal wall and heart with 5/6Nx/NaCl when compared with 5/6Nx/Water. Sodium was stored in the abdominal wall, exerting high-osmotic conditions. Reversal of salt loading reduced macrophage infiltration associated with decreased TonEBP in 5/6Nx/NaCl. Macrophage infiltration associated with fibrosis induced by salt loading was decreased in the 5/6Nx/NaCl/CC chemokine receptor 2 (CCR2, receptor of MCP-1)-deficient mice when compared with 5/6Nx/NaCl/Wild mice, suggesting that CCR2 is required for macrophage infiltration in 5/6Nx with NaCl loading. In cultured mesothelial cells and cardiomyocytes, culture media with high NaCl concentration induced MCP-1, Sgk1 and TonEBP mRNA, all of which were suppressed by TonEBP siRNA, indicating that both MCP-1 and Sgk1 are downstream of TonEBP. Our study indicates that high NaCl intake induces MCP-1 expression leading to macrophage infiltration via the TonEBP-MCP-1 pathway in 5/6Nx/NaCl mice, and that TonEBP has a central role in inflammation in patients with renal failure taking high salt.
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