CCL3L3-null status is associated with susceptibility to systemic lupus erythematosus

Kim, Young‐Ho; Lee, Eunyoung Emily; Sim, Hye-Won; Kang, Eun-Kyung; Won, Yoon-Ho; Lee, Dong-eun; Hong, Kyeong-Man; Song, Yeong‐Wook

doi:10.1038/s41598-021-98531-6

Cited by 4 publications

(1 citation statement)

References 41 publications

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“…36 LAP3 has not been reported to be associated with SLE. Studies have found that the upregulation of LAP3 gene expression in patients with Sjogren's syndrome is associated with the deletion of copy number variation (CNVs) on chromosome 4, and CNV is associated with SLE susceptibility, 37 such as tumor necrosis factor (TNF) on chromosome 6 and small RNA-binding exonuclease protective factor La (SSB) on chromosome 2. This suggests that chromosome CNV deletion may affect the expression of the LAP3 gene.…”

Section: Discussionmentioning

confidence: 99%

Screening biomarkers for systemic lupus erythematosus based on single-cell and bulk RNA sequencing

Yang,

Gan

et al. 2023

Preprint

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Systemic lupus erythematosus (SLE) is an autoimmune disease. The pathogenesis of SLE remains unclear, and the aim of this study was to identify novel biomarkers of SLE. First, key modules and key cell clusters for the trait of sample grouping were screened by weighted gene coexpression network analysis (WGCNA). The differentially expressed genes (DEGs) between SLE and normal samples in GSE72326 were screened. The candidate genes were obtained by overlapping DEGs, key module genes, and the marker genes of key cell clusters. The random forest algorithm was executed based on candidate genes, and the top 5 genes were selected as the hub genes. In addition, gene set enrichment analysis (GSEA) of hub genes was performed. Finally, expression validation, methylation analysis, and immunoinfiltration analysis were completed. A total of 90 DEGs were obtained between SLE and control samples in the GSE72326 dataset. By random forest analysis, the hub genes (TNFSF13B, FCGR1A, TNFSF10, ISG15, LAP3) were obtained. GSEA revealed that TNFSF13B and FCGR1A were involved in primary immunodeficiency, cytosolic DNA sensing pathway, ribosome, and TNFSF10, ISG15, and LAP3 were related to pyruvate metabolism, complement and coagulation cascade. TNFSF13B, FCGR1A, TNFSF10, ISG15, and LAP3 were identified as hub genes of SLE, which provides a new perspective to study SLE. Purpose: Systemic lupus erythematosus (SLE) is an autoimmune disease. The pathogenesis of SLE remains unclear, and the aim of this study was to identify novel biomarkers of SLE. Patients and methods: First, key modules and key cell clusters for the trait of sample grouping were screened by weighted gene coexpression network analysis (WGCNA). The differentially expressed genes (DEGs) between SLE and normal samples in GSE72326 were screened. The candidate genes were obtained by overlapping DEGs, key module genes, and the marker genes of key cell clusters. The random forest algorithm was executed based on candidate genes, and the top 5 genes were selected as the hub genes. In addition, gene set enrichment analysis (GSEA) of hub genes was performed. Finally, expression validation, methylation analysis, and immunoinfiltration analysis were completed. Results: A total of 90 DEGs were obtained between SLE and control samples in the GSE72326 dataset. By random forest analysis, the hub genes (TNFSF13B, FCGR1A, TNFSF10, ISG15, LAP3) were obtained. GSEA revealed that TNFSF13B and FCGR1A were involved in primary immunodeficiency, cytosolic DNA sensing pathway, ribosome, and TNFSF10, ISG15, and LAP3 were related to pyruvate metabolism, complement and coagulation cascade. Conclusion: TNFSF13B, FCGR1A, TNFSF10, ISG15, and LAP3 were identified as hub genes of SLE, which provides a new perspective to study SLE.

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Section: Discussionmentioning

confidence: 99%

Screening biomarkers for systemic lupus erythematosus based on single-cell and bulk RNA sequencing

Yang,

Gan

et al. 2023

Preprint

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Genetic and functional modulation by agonist MRS5698 and allosteric enhancer LUF6000 at the native A3 adenosine receptor in HL-60 cells

Gao,

Chen,

Gao

et al. 2024

Purinergic Signalling

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The A3 adenosine receptor (AR) is an important inflammatory and immunological target. However, the underlying mechanisms are not fully understood. Here, we report the gene regulation in HL-60 cells treated acutely with highly selective A3AR agonist MRS5698, positive allosteric modulator (PAM) LUF6000, or both. Both pro- and anti-inflammatory genes, such as IL-1a, IL-1β, and NFκBIZ, are significantly upregulated. During our observations, LUF6000 alone produced a lesser effect, while the MRS5698 + LUF6000 group demonstrated generally greater effects than MRS5698 alone, consistent with allosteric enhancement. The number of genes up- and down-regulated are similar. Pathway analysis highlighted the critical involvement of signaling molecules, including IL-6 and IL-17. Important upstream regulators include IL-1a, IL-1β, TNF-α, NF-κB, etc. PPAR, which modulates eicosanoid metabolism, was highly downregulated by the A3AR agonist. Considering previous pharmacological results and mathematical modeling, LUF6000’s small enhancement of genetic upregulation suggested that MRS5698 is a nearly full agonist, which we demonstrated in both cAMP and calcium assays. The smaller effect of LUF6000 on MRS5698 in comparison to its effect on Cl-IB-MECA was shown in both HL-60 cells endogenously expressing the human (h) A3AR and in recombinant hA3AR-expressing CHO cells, consistent with its HL-60 cell genetic regulation patterns. In summary, by using both selective agonists and PAM, we identified genes that are closely relevant to immunity and inflammation to be regulated by A3AR in differentiated HL-60 cells, a cell model of neutrophil function. In addition, we demonstrated the previously uncharacterized allosteric signaling-enhancing effect of LUF6000 in cells endogenously expressing the hA3AR.

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Genome-wide identification of copy number variations in wrinkled skin cases of Xiang pigs

Liu,

Hu,

Wang

et al. 2024

Sci Rep

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CCL3L3-null status is associated with susceptibility to systemic lupus erythematosus

Cited by 4 publications

References 41 publications

Screening biomarkers for systemic lupus erythematosus based on single-cell and bulk RNA sequencing

Screening biomarkers for systemic lupus erythematosus based on single-cell and bulk RNA sequencing

Genetic and functional modulation by agonist MRS5698 and allosteric enhancer LUF6000 at the native A3 adenosine receptor in HL-60 cells

Genome-wide identification of copy number variations in wrinkled skin cases of Xiang pigs

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