Dietary High Salt Intake Exacerbates SGK1-Mediated T Cell Pathogenicity in L-NAME/High Salt-Induced Hypertension.
Int J Mol Sci
; 25(8)2024 Apr 16.
Article
em En
| MEDLINE
| ID: mdl-38673987
ABSTRACT
Sodium chloride (NaCl) activates Th17 and dendritic cells in hypertension by stimulating serum/glucocorticoid kinase 1 (SGK1), a sodium sensor. Memory T cells also play a role in hypertension by infiltrating target organs and releasing proinflammatory cytokines. We tested the hypothesis that the role of T cell SGK1 extends to memory T cells. We employed mice with a T cell deletion of SGK1, SGK1fl/fl × tgCD4cre mice, and used SGK1fl/fl mice as controls. We treated the mice with L-NAME (0.5 mg/mL) for 2 weeks and allowed a 2-week washout interval, followed by a 3-week high-salt (HS) diet (4% NaCl). L-NAME/HS significantly increased blood pressure and memory T cell accumulation in the kidneys and bone marrow of SGK1fl/fl mice compared to knockout mice on L-NAME/HS or groups on a normal diet (ND). SGK1fl/fl mice exhibited increased albuminuria, renal fibrosis, and interferon-γ levels after L-NAME/HS treatment. Myography demonstrated endothelial dysfunction in the mesenteric arterioles of SGK1fl/fl mice. Bone marrow memory T cells were adoptively transferred from either mouse strain after L-NAME/HS administration to recipient CD45.1 mice fed the HS diet for 3 weeks. Only the mice that received cells from SGK1fl/fl donors exhibited increased blood pressure and renal memory T cell infiltration. Our data suggest a new therapeutic target for decreasing hypertension-specific memory T cells and protecting against hypertension.
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MEDLINE
Assunto principal:
Proteínas Serina-Treonina Quinases
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Cloreto de Sódio na Dieta
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Proteínas Imediatamente Precoces
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NG-Nitroarginina Metil Éster
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En
Ano de publicação:
2024
Tipo de documento:
Article