Could MicroRNAs be Regulators of Gout Pathogenesis?

Wang, Yangang; Xu, Dongmei; Wang, Bin; Hou, Xu

doi:10.1159/000430176

Cited by 16 publications

(16 citation statements)

References 64 publications

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“…Recently, studies confirmed that miRNAs could regulate IL-1β expression in several ways, thereby affecting inflammatory responses of the body [ 25 – 27 ]. Also, recent research indicates that miRNAs are involved in the development of inflammatory arthritis, including GA [ 8 , 9 , 28 ]. However, according to current literature, no miRNAs have been identified as directly targeting IL-1β.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-488 and -920 regulate the production of proinflammatory cytokines in acute gouty arthritis

Zhou

Wang

et al. 2017

Arthritis Res Ther

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BackgroundGout is considered one of the most painful acute conditions caused by deposition of monosodium urate (MSU) crystals within joints. Recent studies have shown that interleukin (IL)-1β is a key inflammatory mediator in acute gouty arthritis (GA), and its level is regulated by microRNAs (miRNAs). However, the molecular mechanisms of the regulation remain unclear.MethodsA miRNA microarray was used to analyze the miRNA expression profiles in peripheral white blood cells (WBCs) of patients with GA. THP-1 cells were transfected with miRNA mimics, stimulated by MSU crystals, and then subjected to quantitative real-time polymerase chain reaction or Western blot analysis. Levels of IL-1β, IL-8, and tumor necrosis factor (TNF)-α in culture supernatants of THP-1 cells were measured by enzyme-linked immunosorbent assay. A luciferase reporter assay was conducted to confirm the interaction of miRNA and IL-1β 3′-untranslated regions (UTRs).ResultsCombining bioinformatics and miRNA expression profiles, we found five miRNAs (hsa-miR-30c-1-3p, hsa-miR-488-3p, hsa-miR-550a-3p, hsa-miR-663a, and hsa-miR-920) that possibly target IL-1β. Then, we demonstrated that miR-488 and miR-920 were significantly decreased in the WBCs of patients with GA and that MSU crystals could inhibit expression of miR-488 and miR-920. Upregulation of miR-488 and miR-920 could suppress MSU-induced IL-1β protein expression in THP-1 cells, but no significant difference in IL-1β messenger RNA levels was observed. Moreover, we found that miR-488 and miR-920 could directly target the 3′-UTR of IL-1β. Overexpression of miR-488 and miR-920 could significantly inhibit the gene and protein expression of IL-8 and TNF-α in MSU-induced THP-1 cells.ConclusionsThis study demonstrates the roles of miR-488 and miR-920 in regulating the production of proinflammatory cytokines in the pathogenesis of GA. These findings suggest that miR-488 and miR-920 could serve as potential therapeutic targets in the treatment of GA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1418-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-488 and -920 regulate the production of proinflammatory cytokines in acute gouty arthritis

Zhou

Wang

et al. 2017

Arthritis Res Ther

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“…The adhesion of neutrophils to vascular cells, translocation across endothelial cells, and migration toward inflammatory sites is a basic feature of acute inflammation. 7 Translocation of inflammatory cells across the membrane requires intercellular adhesion molecule 1 (ICAM1).…”

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confidence: 99%

Therapeutic Effects of Total Saponins From Dioscorea nipponica Makino on Gouty Arthritis Based on the MAPK-PPARγ Signaling Pathway: An In Vitro Study

Zhou

Zhang

et al. 2020

Natural Product Communications

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Gouty arthritis (GA) is an inflammatory disease caused by the deposition of monosodium urate in the synovial membrane and cartilage due to a high concentration of uric acid in the blood. Dioscorea nipponica Makino is widely used in the clinic to treat GA. Total saponins are its main components and showed an anti-inflammatory effect on GA in a previous study. The mitogen-activated protein kinase (MAPK)-peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway plays a key role during the onset of GA; however, little is known about its potential mechanism. Based on in vitro experiments, this study aims to determine the mechanism of total saponins from Dioscorea nipponica Makino (TDN) in treating GA by regulating the MAPK-PPARγ signaling pathway. Fibroblast-like synoviocytes were divided into 3 groups: the model group, which was given 10 µg/L IL-1β to induce proliferation; TDN group (10 µg/L IL-1β + 100 µg/L TDN); and indomethacin group (10 µg/L IL-1β + 100 µg/L indomethacin). Seventy-two hours after treatment, the real-time PCR method was used to detect the mRNA expression levels of extracellular signal regulated kinase 1/2 (ERK1/2), p-38, c-Jun N-terminal kinase (JNK), IKKα, c-Jun, MAPK phosphatase (MKP), vascular cell adhesion molecule 1 (VCAM1), intercellular adhesion molecule 1 (ICAM1), C-X-C motif chemokine ligand 1 (CXCL1), PPARγ, and Adipor2. The Western blot method was used to detect the protein expression of ERK1/2, p-ERK1/2, p-38, p-P38, JNK, p-JNK, IKKα, p-IKKα, c-Jun, p-c-Jun, MKP, p-MKP, VCAM1, ICAM1, CXCL1, PPARγ, and Adipor2. Compared with the model group, the TDN group displayed significantly increased mRNA expression of c-Jun, MKP, CXCL1, PPARγ, and Adipor2 and significantly decreased mRNA expression of ICAM1. Compared with the model group, the TDN group exhibited significantly increased protein expression of MKP and significantly decreased protein expression of p-ERK1/2, p-38, p-JNK, p-IKKα, p-c-Jun, VCAM1, ICAM1, and PPARγ. Our results indicated that TDN could treat GA by influencing the MAPK-PPARγ signaling pathway.

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“…The uptake of MSU crystals by residual macrophages in inflamed tissue stimulates a series of inflammatory pathways that lead to the local recruitment of leukocytes (chemotaxis), possibly through endothelial activation [68]. Although the involvement of TLRs, NLRP3 inflammasome, and IL-1β in the MSU-induced inflammatory reaction is well-known, there are no miRNAs discovered, thus far, directly targeting TLRs, IL-1β, chemokines, and NLRP3 in gout [69]. …”

Section: Oa and Gouty Arthritis: Overview Of Pathophysiological Fementioning

confidence: 99%

The Role of miRNAs in Common Inflammatory Arthropathies: Osteoarthritis and Gouty Arthritis

2016

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MicroRNAs (miRNAs) are small, non-coding RNA species that are highly evolutionarily conserved, from higher invertebrates to man. Up to 1000 miRNAs have been identified in human cells thus far, where they are key regulators of the expression of numerous targets at the post-transcriptional level. They are implicated in various processes, including cell differentiation, metabolism, and inflammation. An expanding list of miRNAs is known to be involved in the pathogenesis of common, non-autoimmune inflammatory diseases. Interestingly, osteoarthritis (OA) is now being conceptualized as a metabolic disease, as there is a correlation among hyperuricemia and metabolic syndrome (MetS). Experimental evidence suggests that metabolic deregulation is a commonality between these different pathological entities, and that miRNAs are key players in the modulation of metabolic routes. In light of these findings, this review discusses the role of miRNAs in OA and gouty arthritis, as well as the possible therapeutic targetability of miRNAs in these diseases.

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Could MicroRNAs be Regulators of Gout Pathogenesis?

Cited by 16 publications

References 64 publications

MicroRNA-488 and -920 regulate the production of proinflammatory cytokines in acute gouty arthritis

MicroRNA-488 and -920 regulate the production of proinflammatory cytokines in acute gouty arthritis

Therapeutic Effects of Total Saponins From Dioscorea nipponica Makino on Gouty Arthritis Based on the MAPK-PPARγ Signaling Pathway: An In Vitro Study

The Role of miRNAs in Common Inflammatory Arthropathies: Osteoarthritis and Gouty Arthritis

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