Rutin attenuates inflammation by downregulating AGE-RAGE signaling pathway in psoriasis: Network pharmacology analysis and experimental evidence

Wang, Mingxia; Ma, Xiaoxuan; Gao, Chunjie; Luo, Yue; Fei, Xiaoya; Zheng, Qi; Ma, Xin; Kuai, Le; Li, Bin; Wang, Ruiping; Song, Jiankun

doi:10.1016/j.intimp.2023.111033

Cited by 13 publications

(2 citation statements)

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“…Its primary role is to serve as a receptor for advanced glycosylation end products (AGEs) ( 39 ). Upon binding of AGEs to AGER, an enhanced inflammatory response is triggered, leading to the upregulation of various pro-inflammatory cytokines, including NF-κB, TNF-α, IFN-γ, IL-22, IL-6, IL-4, and IL-1β ( 40 – 42 ). Moreover, AGEs have the capability to induce macrophage polarization towards the M1 type through activation of the RAGE/ROS/TLR4/STAT1 signaling pathway ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

“…Upon binding of AGEs to AGER, an enhanced inflammatory response is triggered, leading to the upregulation of various pro-inflammatory cytokines, including NF-κB, TNF-α, IFN-γ, IL-22, IL-6, IL-4, and IL-1β ( 40 – 42 ). Moreover, AGEs have the capability to induce macrophage polarization towards the M1 type through activation of the RAGE/ROS/TLR4/STAT1 signaling pathway ( 40 ). The M1-type macrophages, known for their pronounced pro-inflammatory properties, significantly contribute to the initiation and progression of AS.…”

Section: Discussionmentioning

confidence: 99%

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Proteome-wide Mendelian randomization identifies therapeutic targets for ankylosing spondylitis

Zhao,

Fang,

Lai

et al. 2024

Front. Immunol.

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BackgroundAnkylosing Spondylitis (AS) is a chronic inflammatory disorder which can lead to considerable pain and disability. Mendelian randomization (MR) has been extensively applied for repurposing licensed drugs and uncovering new therapeutic targets. Our objective is to pinpoint innovative therapeutic protein targets for AS and assess the potential adverse effects of druggable proteins.MethodsWe conducted a comprehensive proteome-wide MR study to assess the causal relationships between plasma proteins and the risk of AS. The plasma proteins were sourced from the UK Biobank Pharma Proteomics Project (UKB-PPP) database, encompassing GWAS data for 2,940 plasma proteins. Additionally, GWAS data for AS were extracted from the R9 version of the Finnish database, including 2,860 patients and 270,964 controls. The colocalization analysis was executed to identify shared causal variants between plasma proteins and AS. Finally, we examined the potential adverse effects of druggable proteins for AS therapy by conducting a phenome-wide association study (PheWAS) utilizing the extensive Finnish database in version R9, encompassing 2,272 phenotypes categorized into 46 groups.ResultsThe findings revealed a positive genetic association between the predicted plasma levels of six proteins and an elevated risk of AS, while two proteins exhibited an inverse association with AS risk (Pfdr < 0.05). Among these eight plasma proteins, colocalization analysis identified AIF1, TNF, FKBPL, AGER, ALDH5A1, and ACOT13 as shared variation with AS(PPH3+PPH4>0.8), suggesting that they represent potential direct targets for AS intervention. Further phenotype-wide association studies have shown some potential side effects of these six targets (Pfdr < 0.05).ConclusionOur investigation examined the causal connections between six plasma proteins and AS, providing a comprehensive understanding of potential therapeutic targets.

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