Anti-Double-Stranded DNA IgG Participates in Renal Fibrosis through Suppressing the Suppressor of Cytokine Signaling 1 Signals

Wang, Ping; Yang, Jie; Tong, Fang; Duan, Zhaoyang; Liu, Xingyin; Xia, Linlin; Li, Ké; Xia, Yumin

doi:10.3389/fimmu.2017.00610

Cited by 19 publications

(27 citation statements)

References 48 publications

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“…Systemic lupus erythematosus is characterized by serum positivity of anti-dsDNA autoantibodies, which are produced by B cell-derived plasma cells ( 52 ). Anti-dsDNA autoantibodies are instrumental in LN through recognition of multiple self-antigens and initiation of renal fibrosis ( 53 – 55 ). BAFF, which is a DC- and monocyte-derived cytokine of TNF family, is crucial in regulating B cell maturation, survival, and function ( 56 ).…”

Section: Socs1 Participates In the Hematologic Abnormalities In Slementioning

confidence: 99%

“…In progressive LN, fibrosis is one of the main pathologies, and it contributes to the development of end-stage renal disease, which is evidenced by glomerular sclerosis ( 3 ). Wang et al have demonstrated that SOCS1 expression is decreased in the glomeruli of LN patients and in MRL/lpr mice with anti-dsDNA IgG deposition as compared with their control groups ( 53 ). In MRL/lpr mice, STAT1 is overexpressed in glomerular mesangial, endothelial, and tubular epithelial cells, whereas SOCS1 is downregulated accordingly ( 62 ).…”

Section: Socs1 Inhibition Is Pivotal In the Pathogenesis Of Lnmentioning

confidence: 99%

“…An interesting phenomenon is that anti-dsDNA IgG exhibits nephritogenicity through the blockade of SOCS1 signals. Anti-dsDNA IgG specifically binds to SOCS1-KIR and directly catalyzes KIR ( 53 ). Therefore, anti-dsDNA IgG competes with JAK2 activation loop for KIR, which leads to the blockade of signals from SOCS1 to the JAK2/STAT1 pathway.…”

Section: Socs1 Inhibition Is Pivotal In the Pathogenesis Of Lnmentioning

confidence: 99%

“…Therefore, anti-dsDNA IgG competes with JAK2 activation loop for KIR, which leads to the blockade of signals from SOCS1 to the JAK2/STAT1 pathway. Downstream proinflammatory cytokines and profibrotic factors are upregulated in LN ( 53 ). In addition, ALW, which is a DNA-mimicking peptide with a sequence of ALWPPNLHAWVP, can restore SOCS1 expression by blocking the binding of anti-dsDNA IgG to antigens, thus further suppressing the JAK2/STAT1 pathway and attenuating LN ( 53 , 54 ).…”

Section: Socs1 Inhibition Is Pivotal In the Pathogenesis Of Lnmentioning

confidence: 99%

“…Downstream proinflammatory cytokines and profibrotic factors are upregulated in LN ( 53 ). In addition, ALW, which is a DNA-mimicking peptide with a sequence of ALWPPNLHAWVP, can restore SOCS1 expression by blocking the binding of anti-dsDNA IgG to antigens, thus further suppressing the JAK2/STAT1 pathway and attenuating LN ( 53 , 54 ). These findings suggest that SOCS1 is involved in the nephritogenicity of anti-dsDNA IgG and that SOCS1 upregulation can ameliorate LN.…”

Section: Socs1 Inhibition Is Pivotal In the Pathogenesis Of Lnmentioning

confidence: 99%

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Defective Suppressor of Cytokine Signaling 1 Signaling Contributes to the Pathogenesis of Systemic Lupus Erythematosus

Wang

Xia

2017

Front. Immunol.

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Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving injuries in multiple organs and systems. Exaggerated inflammatory responses are characterized as end-organ damage in patients with SLE. Although the explicit pathogenesis of SLE remains unclear, increasing evidence suggests that dysregulation of cytokine signals contributes to the progression of SLE through the Janus kinase/signal transducer and activator of transcription (STAT) signaling pathway. Activated STAT proteins translocate to the cell nucleus and induce transcription of target genes, which regulate downstream cytokine production and inflammatory cell infiltration. The suppressor of cytokine signaling 1 (SOCS1) is considered as a classical inhibitor of cytokine signaling. Recent studies have demonstrated that SOCS1 expression is decreased in patients with SLE and in murine lupus models, and this negatively correlates with the magnitude of inflammation. Dysregulation of SOCS1 signals participates in various pathological processes of SLE such as hematologic abnormalities and autoantibody generation. Lupus nephritis is one of the most serious complications of SLE, and it correlates with suppressed SOCS1 signals in renal tissues. Moreover, SOCS1 insufficiency affects the function of several other organs, including skin, central nervous system, liver, and lungs. Therefore, SOCS1 aberrancy contributes to the development of both systemic and local inflammation in SLE patients. In this review, we discuss recent studies regarding the roles of SOCS1 in the pathogenesis of SLE and its therapeutic implications.

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Section: Socs1 Participates In the Hematologic Abnormalities In Slementioning

confidence: 99%

Section: Socs1 Inhibition Is Pivotal In the Pathogenesis Of Lnmentioning

confidence: 99%

Section: Socs1 Inhibition Is Pivotal In the Pathogenesis Of Lnmentioning

confidence: 99%

Section: Socs1 Inhibition Is Pivotal In the Pathogenesis Of Lnmentioning

confidence: 99%

Section: Socs1 Inhibition Is Pivotal In the Pathogenesis Of Lnmentioning

confidence: 99%

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Defective Suppressor of Cytokine Signaling 1 Signaling Contributes to the Pathogenesis of Systemic Lupus Erythematosus

Wang

Xia

2017

Front. Immunol.

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Fibroblast growth factor inducible 14 signaling facilitates anti‐dsDNA IgG penetration into mesangial cells

Jia

Ren

et al. 2020

Journal Cellular Physiology

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Anti-double-stranded DNA (dsDNA) antibodies induce renal damage in patients with systemic lupus erythematosus by triggering fibrotic processes in kidney cells. However, the precise mechanism underlying penetration of anti-dsDNA immunoglubolin G (IgG) into cells remains unclear. This study was designed to investigate the effect of tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor inducible 14 (Fn14) signaling on anti-dsDNA IgG penetration into cells. Mesangial cells were cultured in vitro, and stimulated with TWEAK and anti-dsDNA IgG. The results revealed that TWEAK dose-dependently enhanced cellular internalization of anti-dsDNA IgG and the expression of high-mobility group box 1 (HMGB1). In addition, TWEAK and anti-dsDNA IgG synthetically downregulate suppressor of cytokine signaling 1, and induce the expression of various fibrotic factors. Furthermore, inhibition of HMGB1 attenuates the enhancement effect of TWEAK on anti-dsDNA IgG internalization. The TWEAK upregulation of HMGB1 involves the nuclear factor-κB and phosphatidylinositide 3-kinase/protein kinase B pathways. Therefore, TWEAK/ Fn14 signaling contributes to the penetration of anti-dsDNA IgG and relevant fibrotic processes in mesangial cells.

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Mesangial Cells in Lupus Nephritis

Nowling

2021

Curr Rheumatol Rep

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Anti-Double-Stranded DNA IgG Participates in Renal Fibrosis through Suppressing the Suppressor of Cytokine Signaling 1 Signals

Cited by 19 publications

References 48 publications

Defective Suppressor of Cytokine Signaling 1 Signaling Contributes to the Pathogenesis of Systemic Lupus Erythematosus

Defective Suppressor of Cytokine Signaling 1 Signaling Contributes to the Pathogenesis of Systemic Lupus Erythematosus

Fibroblast growth factor inducible 14 signaling facilitates anti‐dsDNA IgG penetration into mesangial cells

Mesangial Cells in Lupus Nephritis

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