Animal models of lupus nephritis: the past, present and a future outlook

Autoimmunity, Год журнала: 2024, Номер 57(1)

Опубликована: Март 13, 2024

Lupus nephritis (LN) is the most severe end-organ pathology in Systemic Erythematosus (SLE). Research has enhanced our understanding of immune effectors and inflammatory pathways LN. However, even with best available therapy, rate complete remission for proliferative LN remains below 50%. A deeper resistance or susceptibility renal cells to injury during progression SLE critical identifying new targets developing effective long-term therapies. The complex heterogeneous nature LN, combined limitations clinical research, make it challenging investigate aetiology this disease directly patients. Hence, multiple murine models resembling SLE-driven are utilised dissect LN's cellular genetic mechanisms, identify therapeutic targets, screen novel compounds. This review discusses commonly used spontaneous inducible mouse that have provided insights into pathogenic mechanisms maintenance therapies

Язык: Английский

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Ferroptosis of CD163+ tissue-infiltrating macrophages and CD10+ PC+ epithelial cells in lupus nephritis

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Июль 31, 2023

Background Dysregulation of cell death and defective clearance dying cells are closely related to the pathogenesis lupus nephritis (LN). However, contribution a recently discovered form programmed (PCD) called ferroptosis LN has not been explored in detail. The purpose this study was investigate role its associated metabolic pathways LN. Methods composite gene expression scores were calculated by averaging z-scored transformed log2 expressed genes within each PCD pathway. Immunohistochemistry immunofluorescence assays used verify bioinformatics results. Results We determined that is prominently specifically elevated glomerular compartment patients compared other forms kidney disease. This finding then verified immunohistochemical staining 4-HNE (a key indicator for ferroptosis) our own cohort (P < 0.0001). Intercorrelation networks observed between blood urea nitrogen, SLE disease activity index, serum creatinine, complement 4, negatively correlated with filtration rate 0.05). Furthermore, enhanced iron metabolism reduced fatty acid synthesis may be most important factors glomerulus. Through analysis single sequencing dataset verification staining, aberrantly activated lipid peroxidation CD163+ macrophages CD10+ PC+ (pyruvate carboxylase) epithelial indicated they undergoing compartment. Conclusions Two dysregulated genes, CD163 PC, identified significantly peroxidation. Targeting provide novel therapeutic approaches

Язык: Английский

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The immunoregulatory roles of non-haematopoietic cells in the kidney

Nature Reviews Nephrology, Год журнала: 2023, Номер 20(4), С. 206 - 217

Опубликована: Ноя. 20, 2023

Язык: Английский

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Serum HMGB-1 released by ferroptosis and necroptosis as a novel potential biomarker for systemic lupus erythematosus

International Immunopharmacology, Год журнала: 2024, Номер 140, С. 112886 - 112886

Опубликована: Авг. 10, 2024

High mobility group box proterin-1 (HMGB-1) is a multifunctional protein that can be released by various programmed cell deaths (PCDs), such as necroptosis and ferroptosis. PCDs play critical role in the pathogenesis of systemic lupus erythematosus (SLE). However, HMGB-1 process SLE remains unclear. This study aims to demonstrate potential diagnosing serum We found levels HMGB-1, receptor-interacting kinase 3 (RIPK3) /mixed lineage domain-like (MLKL) related with necroptosis, metabolites associated ferroptosis were significantly upregulated patients compared HC individuals. These positively correlated disease activity. Additionally, level showed strong positive RIPK3/MLKL metabolites. Moreover, was renal involvement high-antinuclear antibodies (ANA) titer. After interferon γ (IFN-γ) treatment vitro, markers activated HMGB1 both HEK293 HK2 cells. Clinically, considered significant independent risk factor binary logistic assay. Notably, exhibited outstanding diagnostic ability for area under curve (AUC) receiver operating characteristic (ROC) analysis. Taken together, our indicates promising biomarker diagnosis monitoring SLE.

Язык: Английский

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Ferroptosis in hepatocellular carcinoma: Mechanisms and therapeutic implications

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 182, С. 117769 - 117769

Опубликована: Дек. 16, 2024

Язык: Английский

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