Long noncoding RNA SNHG8 accelerates acute gouty arthritis development by upregulating AP3D1 in mice

Abstract

Gout can affect the quality of life of patients due to monosodium urate monohydrate (MSU) crystals. Numerous studies have proposed that long noncoding RNAs (lncRNAs) regulate gout. We aimed to reveal the function of lncRNA small nucleolar RNA host gene 8 (SNHG8) in acute gouty arthritis (GA). A GA mouse model was established by injection of MSU into footpads. The levels of SNHG8, miR-542-3p and adaptor-related protein complex 3 subunit delta 1 (AP3D1) in footpads were detected via polymerase chain reaction analysis. Hematoxylin–eosin staining revealed the paw swelling in mice. Enzyme-linked immunosorbent assay and western blot analysis were applied to determine the concentrations of proinflammatory cytokines. SNHG8 expression was identified to be upregulated after MSU treatment. Ablation of SNHG8 decreased the MSU-induced enhancement of paw swelling and foot thickness. In addition, SNHG8 depletion decreased the protein levels of proinflammatory factors in GA mice. Mechanically, SNHG8 was verified to be a sponge of miR-542-3p, and miR-542-3p targeted AP3D1 3ʹ untranslated region. SNHG8 competitively bound with miR-542-3p to upregulate AP3D1 expression. Finally, results of rescue assays illustrated that AP3D1 upregulation offset the SNHG8-mediated inhibition on paw swelling and protein levels of proinflammatory factors in GA mice. In conclusion, SNHG8 accelerates acute GA development by upregulating AP3D1 in an miR-542-3p-dependent way in mice, providing an effective therapeutic approach to treat acute GA.

Intestinal toxicity alleviation and efficacy potentiation through therapeutic administration of Lactobacillus paracasei GY-1 in the treatment of gout flares with colchicine

“…In addition to IL-1β, two other pro-inflammatory cytokines, IL-6 and TNF-α, have been commonly used to assess the therapeutic effects. 44,45 In line with previous studies, 44,45 their levels were found to be increased in the G-PS mice compared to the NC group (Fig. 6C and D).…”

LncRNA HOTTIP promotes inflammatory response in acute gouty arthritis via miR‐101‐3p/BRD4 axis

“…As a non‐coding RNA, multiple lncRNAs have been identified in AGA in recent years. For example, SNHG8 was aberrantly increased in AGA and promoted mouse AGA progression by regulating miR‐542‐3p/AP3D1 5 . lncRNA‐MM2P is abnormally reduced in MSU‐treated macrophages and participates in the inflammation by regulating macrophage polarization 7 .…”

“…They exert regulatory effects on gene levels and function via the transcriptional level, post‐transcriptional level (affecting protein translation, synthesis, and degradation), and epigenetic level (DNA methylation, acetylation). lncRNAs are emerging as novel biomarkers for disease diagnosis and treatment, and regulating them is a powerful strategy to stop disease progressions, such as SNHG8, 5 H19, 6 and lncRNA‐MM2P 7 . lncRNA HOXA distal transcript antisense RNA (HOTTIP) is located on chromosome 7p15.2.…”

Cynarin suppresses gouty arthritis induced by monosodium urate crystals

“…Gout is a metabolic disease and a common cause of inflammatory arthritis [ 1 , 2 ]. Epidemiological studies show that the prevalence of gout is 0.6% in developed and 1.1% in China [ 3 , 4 ]. The prevalence is 1.5% among men and 0.9% for women [ 4 ].…”

“…Epidemiological studies show that the prevalence of gout is 0.6% in developed and 1.1% in China [ 3 , 4 ]. The prevalence is 1.5% among men and 0.9% for women [ 4 ]. Disorders of the purine catabolic pathway cause hyperuricemia wherein serum urate levels consistently exceed in limit of 7.0 mg/dL [ 2 ].…”