miR‐3146 induces neutrophil extracellular traps to aggravate gout flare

Abstract

Background Gout is an inflammatory arthritis and is characterized by the accumulation of deposited monosodium urate (MSU) crystals in the joints. miRNAs may act as key regulators of gout pathogenesis. 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 gout. Methods The expression of miR‐3146 and sirtuin 1 (SIRT1) was determined by real‐time reverse transcription‐polymerase chain reaction and Western blot, respectively. 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. Gout model was induced in rats to verify the effects of miR‐3146 inhibition on histopathological changes and NETs. Results Here, we found miR‐3146 expression was dramatically increased in neutrophils of patients with gout, which was accompanied with the higher levels of NETs. 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 gout. Conclusion Our findings indicated that miR‐3146‐mediated NETs formation may play a potential role in the pathogenesis of gout. These results suggested that miR‐3146 could be used as a potential therapeutic target for the treatment of gout.

Role of microRNA alternation in the pathogenesis of gouty arthritis

“…Recently, it has been shown that MSU stimulation can significantly increase miR-3146 expression in neutrophils, accompanied by the formation of many NETs. In contrast, treating rats with antagomir-3146 reduced NETs formation and relief of joint swelling and inflammation, suggesting that early NETs formation exacerbates GA and that miR-3146 plays a role vital role before NETs formation ( 83 ). However, the current research on NETs is still inadequate, and how miRNAs regulate the development of NETs in gout is still unclear.…”

Identification of 17 novel epigenetic biomarkers associated with anxiety disorders using differential methylation analysis followed by machine learning-based validation

“…5A, and Additional file 1: Supplementary Text). [44][45][46][47][48][49] In contrast, five genes (MIR3146, ESRRA, SEC23IP, DIP2C, and CPD(SLC6A4)) were directly related to serotonin and GABA neurotransmitters, which are known to be relevant to mood disorders like depression and anxiety (Fig. 5B, and Additional file 1: Supplementary Text).…”

“…5B, and Additional file 1: Supplementary Text). [44,45,[50][51][52][53][54][55][56][57][58][59][60][61][62] It's important to note that previous studies have demonstrated the impact of psychological stress on apoptosis in immune cells within the bloodstream. [63][64][65][66][67][68] This study, through the identification of differential methylation in genes associated with cell stress response, regulation of mitochondrial function, and control of apoptosis in individuals with anxiety disorders, provides support for these previous findings (Fig.…”

Inflammatory microRNAs in cardiovascular pathology: another brick in the wall

“…To date, ten miRNAs (miR-15b-5p ( 100 ), miR-142-3p ( 101 ), miR-144 ( 102 ), miR-146a-5p ( 103 ), miR-155 ( 104 ), mir-223 ( 105 ), miR-378a-3p ( 100 ), miR-505 ( 106 ), miR-3146 ( 107 ), and miR-4512 ( 108 )) have been shown to regulate NETosis in mammals ( 109 ). Three of them are considered inflamma-miRs (miR-146a-5p, miR-155, and miR-223) in the present review and will be briefly described.…”