Exploring the role of LIAS-related cuproptosis in systemic lupus erythematosus DOI Creative Commons
Yan Li, Bojun Xu,

Jimin Zhang

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: May 30, 2023

Abstract Background Cuproptosis is a novel mode of cell death, which strongly related to energy metabolism in mitochondria and regulated by protein lipoylation. Currently, the molecular mechanisms cuproptosis-related genes (CRGs) involved systemic lupus erythematosus (SLE) largely remained unclear, our study aimed explore cuproptosis CRGs SLE. Methods Bulk RNA-seq datasets were collected display expressions peripheral blood mononuclear cells (PBMCs) SLE healthy individuals, then ROC analysis was used establish diagnostic models CRGs. Next, immune infiltration analyses applied reveal difference LIAS-low LIAS-high group. Additionally, WGCNA performed find gene modules significantly corelated with LIAS expression level. We also functional enrichment for LIAS-related determine potential pathways development Finally, scRNA-seq dataset cluster subsets, activated pathways, cell-cell interactions cells. Result found CDKN2A increased decreased patients compared individuals. The AUC score showed that had great value than other results proportion diverse samples. sets level dephosphorylation JAK1 SHP1, phosphorylation STAT2, cytokine signaling system, interferon-alpha beta, inhibition JAK kinase activity SOCS1/3 so on. communication CCL- (CCL5 + CCR1) ANNEXIN- (ANXA1 FPR1) might play an essential role network between Conclusions Above findings inferred LIAS-mediated involve comprehensive cellular mechanism cause occurrence

Language: Английский

Therapeutic potential of MCC950, a specific inhibitor of NLRP3 inflammasome in systemic lupus erythematosus DOI Open Access
Xiaoxiao Wu,

Junhao Yang,

Juanjie Wu

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 172, P. 116261 - 116261

Published: Feb. 9, 2024

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder with pathogenesis that remains incompletely understood, resulting in limited treatment options. MCC950, highly specific NLRP3 inflammasome inhibitor, effectively suppresses the activation of NLRP3, thus reducing production caspase-1, pro-inflammatory cytokines IL-1β and IL-18. This review highlights pivotal role pathways SLE discusses potential therapeutic application MCC950 SLE. Notably, it comprehensively elucidates mechanism targeting pathway treatment, outlining its regulating autophagy necroptosis. The insights gained contribute to deeper understanding value therapy, serving as robust foundation for further research clinical applications.

Language: Английский

Citations

10
C5a-C5aR1 axis controls mitochondrial fission to promote podocyte injury in lupus nephritis DOI Creative Commons

Baokui Ye,

Binfeng Chen, Chaohuan Guo

et al.

Molecular Therapy, Journal Year: 2024, Volume and Issue: 32(5), P. 1540 - 1560

Published: March 6, 2024

Language: Английский

Citations

9
Molecular characterization of PANoptosis-related genes with features of immune dysregulation in systemic lupus erythematosus DOI
Wei Sun, Pengchong Li, Min Wang

et al.

Clinical Immunology, Journal Year: 2023, Volume and Issue: 253, P. 109660 - 109660

Published: June 7, 2023

Language: Английский

Citations

21
Identification and validation of key autophagy-related genes in lupus nephritis by bioinformatics and machine learning DOI Creative Commons
Su Zhang,

Weitao Hu,

Young Tang

et al.

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(1), P. e0318280 - e0318280

Published: Jan. 27, 2025

Lupus nephritis (LN) is one of the most frequent and serious organic manifestations systemic lupus erythematosus (SLE). Autophagy, a new form programmed cell death, has been implicated in variety renal diseases, but relationship between autophagy LN remains unelucidated. We analyzed differentially expressed genes (DEGs) kidney tissues from 14 patients 7 normal controls using GSE112943 dataset. Key modules their contained were identified utilizing weighted gene co-expression network analysis (WGCNA). Differentially autophagy-related (DE-ARGs) among DEGs, key module (ARGs) obtained by venn plot, subjected to protein-protein interaction construction. Two machine learning methods applied identify signature genes. The area under receiver operating characteristic (ROC) curves was used assess accuracy also immune infiltration LN. Additionally, association diseases predicted. Finally, expression verified clinical samples animal experiments. A total 10304 DEGs GSE1129943 29 WGCNA. Among them, brown coral 2 exhibited significant correlation with (cor = 0.86, -0.84, p<0.001). Machine techniques 5 genes, only validated external dataset GSE32591, namely MAP1LC3B (AUC 0.920) TNFSF10 0.937), which are involved apoptosis. Immune suggested that these may be associated In addition, have linked mice. These potential provide insights into molecular diagnosis treatment

Language: Английский

Citations

0
Intricating connections: the role of ferroptosis in systemic lupus erythematosus DOI Creative Commons

Guowang Zhao,

Xinghai Li, Ying Zhang

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 4, 2025

Systemic lupus erythematosus (SLE) is a chronic inflammatory and autoimmune disease with multiple tissue damage. However, the pathology remains elusive, effective treatments are lacking. Multiple types of programmed cell death (PCD) implicated in SLE progression have recently been identified. Although ferroptosis, an iron-dependent form death, has numerous pathophysiological features similar to those SLE, such as intracellular iron accumulation, mitochondrial dysfunction, lipid metabolism disorders concentration damage associated-molecular patterns (DAMPs), only few reports demonstrated that ferroptosis involved role pathogenesis continues be neglected. Therefore, this review elucidates potential intricate relationship between provide reliable theoretical basis for further research on SLE.

Language: Английский

Citations

0
Identification of mitochondrial function and programmed cell death associated key biomarkers and the circRNA-miRNA-mRNA regulatory network in systemic lupus erythematosus DOI Creative Commons

Junjie Cao,

Aifang Li, Hui Zhou

et al.

Frontiers in Molecular Biosciences, Journal Year: 2025, Volume and Issue: 12

Published: April 14, 2025

Objectives Systemic Lupus Erythematosus (SLE) is a highly heterogeneous autoimmune disease with complex pathogenic mechanisms. Mitochondrial function and programmed cell death (PCD) play important roles in SLE. This study aims to screen biomarkers related mitochondrial SLE analyze their underlying Methods SLE-related databases were derived from the GEO database, where three merged into one database as training set. Genes PCD sourced MitoCarta 3.0 database. Key genes identified through bioinformatics machine learning, expression levels diagnostic efficacy validated using two datasets validation The relationship between immune cells was analyzed CIBERSORT infiltration analysis. Diagnostic genes-related miRNAs predicted online databases. Differential circRNAs screened circRNA datasets, circbank, finally constructing circRNA-miRNA-mRNA ceRNA regulatory network. Results From 448 differential set, key genes, IFI27 LAMP3, learning WGCNA. Enrichment analysis revealed that they mainly enriched pathways such cycle, systemic lupus erythematosus, cytosolic DNA sensing pathway, toll-like receptor (TLR) signaling pathway nod-like (NLR) pathway. Immune found compared normal group, 11 differentially expressed, 9 types of LAMP3 10 cells. final constructed network consists 2 mRNAs, 5 miRNAs, 4 circRNAs. Conclusion Our ultimately (IFI27 LAMP3) an role In future, have potential become diagnosis treatment Their response may provide new strategies for

Language: Английский

Citations

0
Bioinformatic analysis and experimental verification reveal expansion of monocyte subsets with an interferon signature in systemic lupus erythematosus patients DOI Creative Commons

Jimin Zhang,

Wuwei Zhuang,

Li Y

et al.

Arthritis Research & Therapy, Journal Year: 2025, Volume and Issue: 27(1)

Published: April 25, 2025

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by chronic inflammation and multi-organ damage. A central factor in SLE pathogenesis the excessive production of type I interferon (IFN-I), which drives immune dysregulation. Monocytes, key components system, significantly contribute to IFN-I production. However, their specific roles remain incompletely understood. This study utilized bioinformatics statistical analyses, including robust rank aggregation (RRA), DESeq2, limma, analyze transcriptome data from peripheral blood mononuclear cells (PBMCs) monocytes patients healthy controls. Single-cell RNA sequencing (scRNA-seq) were processed using Seurat R package identify characterize monocyte subsets with strong IFN-driven gene signature. Flow cytometry was employed validate findings, markers such as CD14, SIGLEC1, IRF7 confirm subset composition. Our research has found that undergo transcriptional reprogramming, upregulation signature genes (ISGs), forming SLE-Related Monocyte Signature (SLERRAsignature). Moreover, composition phagocyte changes, an increase trend proportion CD14Mono8 flare group. The differentially expressed (DEGs) 13 are mainly ISGs, expression ISGs higher severe patients. We identified SIGLEC1+IRF7+ among these for first time discovered this group individuals. In SLE, enrichment score set representing positively correlated severity SLE. Finally, flow confirmed frequency CD14+SIGLEC1+IRF7+ PBMCs compared expansion IFN-I-producing subsets, particularly subset, plays crucial role pathogenesis. may serve potential biomarker therapeutic target managing

Language: Английский

Citations

0
Modes and Mechanisms of Salivary Gland Epithelial Cell Death in Sjogren's Syndrome DOI

Jiannan Zhou,

Janak L. Pathak, Qianwen Liu

et al.

Advanced Biology, Journal Year: 2023, Volume and Issue: 7(12)

Published: July 6, 2023

Abstract Sjogren's syndrome is an autoimmune disease in middle and old‐aged women with a dry mucosal surface, which caused by the dysfunction of secretory glands, such as oral cavity, eyeballs, pharynx. Pathologically, are characterized lymphocyte infiltration into exocrine glands epithelial cell destruction autoantibodies Ro/SSA La/SSB. At present, exact pathogenesis unclear. Evidence suggests death subsequent salivary main causes xerostomia. This review summarizes modes gland their role progression. The molecular mechanisms involved during potential leads to treating also discussed.

Language: Английский

Citations

9
CSNK1A1/CK1α suppresses autoimmunity by restraining the CGAS-STING1 signaling DOI
Mingyu Pan,

Tongyu Hu,

Jiao Lyu

et al.

Autophagy, Journal Year: 2023, Volume and Issue: 20(2), P. 311 - 328

Published: Sept. 18, 2023

STING1 (stimulator of interferon response cGAMP interactor 1) is the quintessential protein in CGAS-STING1 signaling pathway, crucial for induction type I IFN (interferon) production and eliciting innate immunity. Nevertheless, overactivation or sustained activation has been closely associated with onset autoimmune disorders. Notably, majority these disorders manifest as an upregulated expression interferons IFN-stimulated genes (ISGs). Hence, strict regulation activity paramount to preserve immune homeostasis. Here, we reported that CSNK1A1/CK1α, a serine/threonine kinase, was essential prevent STING1-mediated through autophagic degradation STING1. Mechanistically, CSNK1A1 interacted upon pathway promoted by enhancing phosphorylation SQSTM1/p62 at serine 351 (serine 349 human), which critical SQSTM1-mediated degradation. Consistently, SSTC3, selective agonist, significantly attenuated promoting Importantly, pharmacological using SSTC3 markedly repressed systemic autoinflammatory responses trex1-/- mouse disease model effectively suppressed IFNs ISGs PBMCs SLE patients. Taken together, our study reveals novel regulatory role maintain Manipulating might be potential therapeutic strategy alleviating aberrant diseases.

Language: Английский

Citations

9
Serum HMGB-1 released by ferroptosis and necroptosis as a novel potential biomarker for systemic lupus erythematosus DOI Creative Commons

Guowang Zhao,

Xingzi Wang,

Hongtao Lei

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 140, P. 112886 - 112886

Published: Aug. 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.

Language: Английский

Citations

3