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Dietary High Salt Intake Exacerbates SGK1-Mediated T Cell Pathogenicity in L-NAME/High Salt-Induced Hypertension.

التفاصيل البيبلوغرافية
العنوان: Dietary High Salt Intake Exacerbates SGK1-Mediated T Cell Pathogenicity in L-NAME/High Salt-Induced Hypertension.
المؤلفون: Maaliki D; Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon., Itani M; Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon., Jarrah H; Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon., El-Mallah C; Department of Nutrition and Food Sciences, Faculty of Agricultural and Food Sciences, American University of Beirut, Beirut 1107, Lebanon., Ismail D; Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon., El Atie YE; Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon., Obeid O; Department of Nutrition and Food Sciences, Faculty of Agricultural and Food Sciences, American University of Beirut, Beirut 1107, Lebanon., Jaffa MA; Epidemiology and Population Health Department, Faculty of Health Sciences, American University of Beirut, Beirut 1107, Lebanon., Itani HA; Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut 1107, Lebanon.; Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2024 Apr 16; Vol. 25 (8). Date of Electronic Publication: 2024 Apr 16.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Hypertension*/chemically induced , Hypertension*/metabolism , Hypertension*/pathology , Immediate-Early Proteins*/metabolism , Immediate-Early Proteins*/genetics , NG-Nitroarginine Methyl Ester*/pharmacology , Protein Serine-Threonine Kinases*/metabolism , Protein Serine-Threonine Kinases*/genetics , Sodium Chloride, Dietary*/adverse effects, Animals ; Male ; Mice ; Blood Pressure/drug effects ; Kidney/metabolism ; Kidney/pathology ; Mice, Inbred C57BL ; Mice, Knockout ; T-Lymphocytes/metabolism ; T-Lymphocytes/immunology
مستخلص: 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, SGK1 fl/fl × tgCD4 cre mice, and used SGK1 fl/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 SGK1 fl/fl mice compared to knockout mice on L-NAME/HS or groups on a normal diet (ND). SGK1 fl/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 SGK1 fl/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 SGK1 fl/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.
Competing Interests: None of the authors have any commercial or financial relationships that can be perceived as conflicts of interest.
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معلومات مُعتمدة: M0048845 American Society of Nephrology
فهرسة مساهمة: Keywords: SGK1; T-lymphocytes; hypertension; immunologic memory; inflammation; memory T cells
المشرفين على المادة: 0 (serum-glucocorticoid regulated kinase)
تواريخ الأحداث: Date Created: 20240427 Date Completed: 20240427 Latest Revision: 20240520
رمز التحديث: 20240520
مُعرف محوري في PubMed: PMC11050194
DOI: 10.3390/ijms25084402
PMID: 38673987
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms25084402