MiR-3146 Induces Neutrophil Extracellular Traps to Aggravate Acute Gouty Arthritis

Abstract

MiR-3146 plays an important role in the formation of neutrophil extracellular traps (NETs) during the pathogenesis of acute gouty arthritis (AGA).The aim of our study was to explore the underlying role and molecular mechanism of miR-3146 in the formation of neutrophil extracellular traps (NETs) during the pathogenesis of acute gouty arthritis (AGA). The expression of miR-3146 and sirtuin 1 (SIRT1) was determined by real-time PCR and western blot. The luciferase reporter assay was performed to identify the targeting relationship between miR-3146 and SIRT1. Reactive oxygen species (ROS) production was detected by fluorescent staining. NETs formation was demonstrated via immunofluorescence staining and ELISA method. AGA model was induced in rats to verify the effects of miR-3146 inhibition on histopathological changes and NETs. Here, we found miR-3146 expression was dramatically increased in neutrophils of patients with AGA, presenting higher levels of NETs. Monosodium urate (MSU) crystals significantly increased miR-3146 expression and ROS production in neutrophils. The NETs process was also triggered by MSU crystals. Furthermore, we verified the interaction between miR-3146 and SIRT1. Additionally, antagomir-3146-based therapy effectively inhibited the formation of NETs in rats with AGA. MiR-3146-mediated NETs formation may play a potential role in the pathogenesis of AGA.