Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs

Jing, Weiyao; Liu, Cui; Chenghong, Su; Limei, Liu; Chen, Ping; Li, Xiangjun; Xinghua, Zhang; Yuan, Bo; Wang, Haidong; Xiaozheng, Du

doi:10.3389/fimmu.2023.1107670

Cited by 25 publications

(16 citation statements)

References 304 publications

(315 reference statements)

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“…This endoplasmic reticulum stress may promote the progression of RA through the proliferation of synovial cells and the production of pro-inflammatory cytokines ( de Seabra Rodrigues Dias et al, 2021 ; Floudas et al, 2022 ; Miglioranza Scavuzzi and Holoshitz, 2022 ). Wulf et al pointed out that oxidative stress in mitochondria can produce many reactive oxygen species (ROS) ( Jing et al, 2023 ). At high concentrations, free radicals and their derivatives are harmful to the organism and destroy all the main components of the cell.…”

Section: Discussionmentioning

confidence: 99%

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RETRACTED: Bioinformatics analysis based on crucial genes of endothelial cells in rheumatoid

Zhou

2023

Front. Genet.

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Objectives: Synovial neovascularization is an early and remarkable event that promotes the development of rheumatoid arthritis (RA) synovial hyperplasia. This study aimed to find potential diagnostic markers and molecular therapeutic targets for RA at the mRNA molecular level.Method: We download the expression profile dataset GSE46687 from the gene expression ontology (GEO) microarray, and used R software to screen out the differentially expressed genes between the normal group and the disease group. Then we performed functional enrichment analysis, used the STRING database to construct a protein-protein interaction (PPI) network, and identify candidate crucial genes, infiltration of the immune cells and targeted molecular drug.Results: Rheumatoid arthritis datasets included 113 differentially expressed genes (DEGs) including 104 upregulated and 9 downregulated DEGs. The enrichment analysis of genes shows that the differential genes are mainly enriched in condensed chromosomes, ribosomal subunits, and oxidative phosphorylation. Through PPI network analysis, seven crucial genes were identified: RPS13, RPL34, RPS29, RPL35, SEC61G, RPL39L, and RPL37A. Finally, we find the potential compound drug for RA.Conclusion: Through this method, the pathogenesis of RA endothelial cells was further explained. It provided new therapeutic targets, but the relationship between these genes and RA needs further research to be validated in the future.

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Section: Discussionmentioning

confidence: 99%

“…This Floudas et al, 2022;Miglioranza Scavuzzi and Holoshitz, 2022). Wulf et al pointed out that oxidative stress in mitochondria can produce many reactive oxygen species (ROS) (Jing et al, 2023). At high concentrations, free radicals and their derivatives are harmful to the organism and destroy all the main components of the cell.…”

Section: Figurementioning

confidence: 99%

RETRACTED: Bioinformatics analysis based on crucial genes of endothelial cells in rheumatoid

Zhou

2023

Front. Genet.

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“…It represents a potential clinical marker for mitochondrial and cellular damage 89 . Mitochondrial failure, accompanied by inadequate energy supply and increased oxidative stress, exists in RA 79,80,90,91 (Table 2), in T1DM 80,92 (Table 2) and in AU 93 (Table 2). Moreover, the mitochondrial Cytochrome c is affected in RA 94,95 , T1DN 96,97 (Table 2) and in AU 98 (Table 2).…”

Section: Discussionmentioning

confidence: 99%

Cross-Reactivity and sequence similarity between microbial transglutaminase and human antigens: expanded exposome of autoimmune diseases

Lerner

Benzvi

Vojdani

2023

Preprint

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Microbial transglutaminase (mTG) is a bacterial survival factor, frequently used as a food additive to glue processed nutrients. As a result, new immunogenic epitopes are generated that might drive autoimmunity. Presently, its contribution to autoimmunity through epitope similarity and cross-reactivity was investigated. Emboss Matcher was used to perform sequence alignment between mTG and various antigens implicated in many autoimmune diseases. Monoclonal and polyclonal antibodies made specifically against mTG were applied to 77 different human tissue antigens using ELISA. Six antigens were detected to share significant homology with mTG immunogenic sequences, representing major targets of common autoimmune conditions. Polyclonal antibody to mTG reacted significantly with 17 out of 77 tissue antigens. This reaction was most pronounced with mitochondrial M2, ANA, and extractable nuclear antigens. The results indicate that sequence similarity and cross-reactivity between mTG and various tissue antigens are possible, supporting the relationship between mTG and the development of autoimmune disorders. 150W

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“…6 Fibroblast-like synoviocytes (FLS) are the primary effect cells sustaining joint inflammation, angiogenesis, and cartilage destruction. 7 During RA activity, FLS produces a multitude of angiogenic factors, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which pathologically alter endothelial cell activity and promote joint angiogenesis. This exacerbates RA severity by contributing to synovial hyperplasia and inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…Angiogenesis is crucial for various physiological processes, including embryonic development, wound healing, and tissue regeneration, as well as pathophysiological conditions like cancer and inflammation 6 . Fibroblast‐like synoviocytes (FLS) are the primary effect cells sustaining joint inflammation, angiogenesis, and cartilage destruction 7 . During RA activity, FLS produces a multitude of angiogenic factors, including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), which pathologically alter endothelial cell activity and promote joint angiogenesis.…”

Section: Introductionmentioning

confidence: 99%

LncRNA HOTAIR regulates the PI3K/AKT pathway via the miR‐126‐3p/PIK3R2 axis to participate in synovial angiogenesis in rheumatoid arthritis

Liu,

Wang,

Huang

et al. 2023

Immunity Inflam & Disease

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BackgroundThe abnormal expression of long noncoding RNA (LncRNA) HOTAIR has been associated with synovial angiogenesis in rheumatoid arthritis (RA). The aim of this study is to investigate whether LncRNA HOTAIR plays a role in synovial angiogenesis in RA by regulating the phosphoinositide 3‐kinase/protein kinase B (PI3K/AKT) pathway through the miR‐126‐3p/PIK3R2 axis.MethodsIn this study, we conducted in vitro experiments by designing overexpression plasmids and small interfering RNAs targeting LncRNA HOTAIR and then transfected them into rheumatoid arthritis fibroblast‐like synoviocytes (RA‐FLS). We then co‐cultured the RA‐FLS with human umbilical vein endothelial cells (HUVEC) to establish a RA‐FLS‐induced HUVEC model. We investigated the effects of LncRNA HOTAIR on the proliferation, migration, lumen forming ability of HUVEC, as well as the expression of synovial endothelial cell markers, angiogenic factors, and the PI3K/AKT pathway. To validate the interactions between LncRNA HOTAIR, miR‐126‐3p, and PIK3R2, we used bioinformatics and luciferase reporter experiments. We also employed real‐time fluorescence quantitative, Western blotanalysis, and immunofluorescence techniques to analyze the target genes and proteins.ResultsThe expression of LncRNA HOTAIR was upregulated in HUVEC induced by RA‐FLS. The overexpression of LncRNA HOTAIR significantly increased the expression of vascular endothelial growth factor, basic fibroblast growth factor, CD34, and CD105 in HUVEC, promoting their proliferation, migration, and lumen formation. At the same time, the overexpression of LncRNA HOTAIR inhibited the expression of miR‐126‐3p, promoted the expression of PIK3R2, activated the PI3K/AKT pathway, and promoted the expression of PI3K, AKT and phosphorylated‐AKT, while the silence of LncRNA HOTAIR reversed these expressions. Bioinformatics and double luciferase reporter gene experiments confirmed the targeting relationship among LncRNA HOTAIR, miR‐126‐3p, and PIK3R2. Finally, the rescue experiments showed that PI3K agonists could reverse the inhibitory effect of silent LncRNA HOTAIR on HUVEC.ConclusionLncRNA HOTAIR has the potential to activate the PI3K/AKT pathway, likely through the regulatory axis involving miR‐126‐3p/PIK3R2, consequently contributing to synovial angiogenesis in RA.

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Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs

Cited by 25 publications

References 304 publications

RETRACTED: Bioinformatics analysis based on crucial genes of endothelial cells in rheumatoid

RETRACTED: Bioinformatics analysis based on crucial genes of endothelial cells in rheumatoid

Cross-Reactivity and sequence similarity between microbial transglutaminase and human antigens: expanded exposome of autoimmune diseases

LncRNA HOTAIR regulates the PI3K/AKT pathway via the miR‐126‐3p/PIK3R2 axis to participate in synovial angiogenesis in rheumatoid arthritis

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