Fumarate modulates phospholipase A2 receptor autoimmunity-induced podocyte injury in membranous nephropathy

Jo, Hyung Ah; Hyeon, Jin Seong; Yang, Seung Hee; Jung, Youngae; Ha, Hunjoo; Jeong, Chang Wook; Kwak, Cheol; Kim, Yaerim; Lee, Hajeong; Lee, Jung Pyo; Joo, Kwon Wook; Lim, Chun Soo; Hwang, Geum‐Sook; Kim, Yon Su

doi:10.1016/j.kint.2020.06.031

Cited by 19 publications

(19 citation statements)

References 47 publications

(50 reference statements)

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“…The nuclear magnetic resonance (NMR)-based urine metabolomic profiling method has been previously published, and details are explained in the Supplemental Methods, Figures S1 and S2. 8…”

Section: Urine Metabolomic Profilingmentioning

confidence: 99%

“…As the prognosis of IgAN is heterogeneous among patients, recent studies have attempted to identify predictive measures for the prognosis of IgAN 4 . Recently, metabolomics has been shown to identify biomarkers in diverse kidney diseases 5‐8 . The metabolomic profile, which is a consequence of one's genomic‐transcriptomic‐proteomic processes and the environmental influence, may be a potential phenotype that reflects the status of complex kidney diseases.…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive metabolomic profiling in early IgA nephropathy patients reveals urine glycine as a prognostic biomarker

Park

Lee

Yang

et al. 2021

J Cellular Molecular Medi

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“…The nuclear magnetic resonance (NMR)-based urine metabolomic profiling method has been previously published, and details are explained in the Supplemental Methods, Figures S1 and S2. 8…”

Section: Urine Metabolomic Profilingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comprehensive metabolomic profiling in early IgA nephropathy patients reveals urine glycine as a prognostic biomarker

Park

Lee

Yang

et al. 2021

J Cellular Molecular Medi

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“…PLA 2 R was used for the diagnosis and monitoring of MN, whereas the underlying mechanisms of PLA 2 R-related MN remain unclear. In urine, Kim et al investigated metabolomic profiles of PLA 2 R-related MN patients with biopsy-proven with those of patients with minimal alteration disease and to healthy controls ( Jo et al, 2021 ). Fumarate was identified as a significant altered metabolite in PLA 2 R-related MN compared with minimal change disease.…”

Section: Systems Biology-based Mechanisms In Imnmentioning

confidence: 99%

Membranous nephropathy: Systems biology-based novel mechanism and traditional Chinese medicine therapy

Miao

Zhang

et al. 2022

Front. Pharmacol.

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Membranous nephropathy (MN) is a renal-limited non-inflammatory autoimmune disease in the glomerulus, which is the second or third main cause of end-stage kidney diseases in patients with primary glomerulonephritis. Substantial achievements have increased our understanding of the aetiology and pathogenesis of murine and human MN. The identification of nephritogenic autoantibodies against neutral endopeptidase, phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) antigens provide more specific concept-driven intervention strategies for treatments by specific B cell-targeting monoclonal antibodies to inhibit antibody production and antibody-antigen immune complex deposition. Furthermore, additional antibody specificities for antigens have been discovered, but their pathogenic effects are uncertain. Although anti-PLA2R and anti-THSD7A antibodies as a diagnostic marker is widely used in MN patients, many questions including autoimmune response development, antigenic epitopes, and podocyte damage signalling pathways remain unresolved. This review describes the current available evidence regarding both established and novel molecular mechanisms based on systems biology approaches (gut microbiota, long non-coding RNAs, metabolite biomarkers and DNA methylation) in MN, with an emphasis on clinical findings. This review further summarizes the applications of traditional Chinese medicines such as Tripterygium wilfordii and Astragalus membranaceus for MN treatment. Lastly, this review considers how the identification of novel antibodies/antigens and unresolved questions and future challenges reveal the pathogenesis of MN.

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“…The media consisted of DMEM/F12 (Lonza) supplemented with 15% fetal bovine serum (FBS, Gibco, Thermo Fisher Scienti c, Waltham, MA), 1× insulin-transferrin-selenium (Gibco), HEPES buffer (10 mmol, Sigma-Aldrich), L-glutamine (200 µmol, Gibco), hydrocortisone (50 nmol, Sigma-Aldrich), penicillin (100 U/mL, Gibco) and streptomycin (100 pg/mL, Gibco) and was changed every 3 days. Plating was performed on plastic dishes coated with bronectin (10 µg/mL, Sigma-Aldrich) 14,15 .…”

Section: Primary Cultured Human Podocytesmentioning

confidence: 99%

Metabolomic profiling in kidney cells treated with a sodium glucose-cotransporter 2 inhibitor

Seo

Lee

et al. 2022

Preprint

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We aimed to determine the metabolomic profile of kidney cells under high glucose conditions and following sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment. Targeted metabolomics using the Absolute IDQ-p180 kit was applied to quantify metabolites in kidney cells stimulated with high glucose (25 and 50 mM) and treated with SGLT2 inhibitor, dapagliflozin (2 µM). Primary cultured human tubular epithelial cells, podocytes, and glomerular endothelial cells were used to identify the metabolomic profile in high glucose conditions following dapagliflozin treatment. The levels of asparagine, PC ae C34:1, and PC ae C36:2 were elevated in tubular epithelial cells stimulated with 50 mM glucose and were significantly decreased after 2 µM dapagliflozin treatment. The level of PC aa C32:0 was significantly decreased after 50 mM glucose treatment compared with the control, and its level was significantly increased after dapagliflozin treatment in podocytes. The level of arginine in glomerular endothelial cells was decreased after stimulation with 50 mM glucose, whereas dapagliflozin treatment significantly elevated its level. The differentially expressed metabolites in kidney cells stimulated by the SGLT2 inhibitor under high glucose conditions were distinct according to cell types.

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Fumarate modulates phospholipase A2 receptor autoimmunity-induced podocyte injury in membranous nephropathy

Cited by 19 publications

References 47 publications

Comprehensive metabolomic profiling in early IgA nephropathy patients reveals urine glycine as a prognostic biomarker

Comprehensive metabolomic profiling in early IgA nephropathy patients reveals urine glycine as a prognostic biomarker

Membranous nephropathy: Systems biology-based novel mechanism and traditional Chinese medicine therapy

Metabolomic profiling in kidney cells treated with a sodium glucose-cotransporter 2 inhibitor

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