title: Exacerbation of lupus nephritis by high sodium chloride related to activation of SGK1 pathway.
abstract: The objective of this study is to explore the effects of high salt diet (HSD) on the severity of lupus nephritis (LN) and its mechanism. MRL/lpr mice were randomly divided into two groups, which were fed with normal diet or sodium-rich chow and tap. C57BL/6 mice were selected as control. Spleen Th1, Th2, Th17 and Treg cells were detected by flow cytometry. Serum TGF-β and IL-17 were measured by enzyme-linked immunosorbent assay. CD4(+) T cells from Systemic Lupus Erythematosus (SLE) patients and healthy donors were treated by NaCl with or without SGK1 inhibitor. Then, Th17 and Treg cells were detected. The HSD MRL/lpr mice had decreased survival rate and increased disease severity. The frequencies of Th1 and Th17 cells increased in HSD treatment group. The ratios of Th1/Th2 and Th17/Treg in HSD treated MRL/lpr mice significantly increased. Serum TGF-β increased after HSD treatment. In vitro, high salt could up-regulate Th17 cells of CD4(+) T cells. The effects of high salt treatment on CD4(+) T cells were reversed by SGK1 inhibitor. Our findings demonstrated that excessive intake of salt in diet is an aggravating factor for LN. High salt diet may deteriorate LN through SGK1 pathway.
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 China.
authors.forename: Genhong
authors.initials: G
authors.lastname: Yao
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 China.
authors.forename: Xuebing
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008 China. Electronic address: lingyunsun@nju.edu.cn.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Sun
mesh_terms: D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D008180:Lupus Erythematosus, Systemic / Q000473:pathology; D008181:Lupus Nephritis / Q000473:pathology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D012965:Sodium Chloride / Q000633:toxicity*; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*; D050378:T-Lymphocytes, Regulatory; D058504:Th17 Cells; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D016207:Cytokines; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D012965:Sodium Chloride; D017673:Sodium Chloride, Dietary; D000099184:Serum-Glucocorticoid Regulated Kinases
keywords: High salt diet; Lupus nephritis; Serum and glucocorticoid-inducible serine/threonine protein kinase 1