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Circular RNA circHIPK3 Activates Macrophage NLRP3 Inflammasome and TLR4 Pathway in Gouty Arthritis via Sponging miR-561 and miR-192

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Abstract

Increasing evidences indicate that circular RNAs (circRNAs) play important roles in regulating gene expressions in various diseases. However, the role of circRNAs in inflammatory response of gouty arthritis remains unknown. This study aims to investigate the role and underlying mechanism of circHIPK3 in inflammatory response of gouty arthritis. Quantitative real-time PCR was used to detect the expressions of circHIPK3, miR-192 and miR-561. Western blot was used to detect the protein levels of TLR4, NLRP3, nuclear factor-κB (NF-κB) related proteins, and Caspase-1. Dual luciferase reporter assay, RNA pull-down assay, and FISH assay were used to confirm the interaction between circHIPK3 and miR-192/miR-561. ELISA was used to detect interleukin (IL)-1β and tumor necrosis factor (TNF)-α levels. circHIPK3 was elevated in synovial fluid mononuclear cells (SFMCs) from patients with gouty arthritis and monosodium urate (MSU)-stimulated THP-1 cells. circHIPK3 overexpression promoted the inflammatory cytokines levels in MSU-stimulated THP-1 cells, and circHIPK3 silencing obtained the opposite effect. Mechanistically, circHIPK3 sponged miR-192 and miR-561, and subsequently promoted the expressions of miR-192 and miR-561 target gene TLR4 and NLRP3. In vivo experiments confirmed circHIPK3 knockdown suppressed gouty arthritis. circHIPK3 sponges miR-192 and miR-561 to promote TLR4 and NLRP3 expressions, thereby promoting inflammatory response in gouty arthritis.

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Data Availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by Joint project of Medical Science and Technology Key Program of Henan Province (Grant No. 2018020122).

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, The First Affiliated Hospital of Zhengzhou University, No. 1, Jianshe East Road, Zhengzhou, 450052, Henan Province, China

    Chaofeng Lian, Jinlei Sun, Wenjuan Guan, Lei Zhang, Xin Zhang, Lu Yang & Wenlu Hu

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  1. Chaofeng Lian
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  2. Jinlei Sun
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  3. Wenjuan Guan
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  4. Lei Zhang
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Contributions

C L performed the experiments, analyzed the data, wrote the paper, and contributed to the conception of the study; J S, W G, and L Z participated in the execution of the experiment; X Z, L Y, and W H contributed to analysis and manuscript preparation.

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Correspondence to Chaofeng Lian.

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Ethics Approval and Consent to Participate

This study was approved by the Ethics Committee of The First Affiliated Hospital of Zhengzhou University. All patients signed informed consent. All animal experiments were complied with the ARRIVE guidelines and were carried out in accordance with the US Public Health Service Policy on Humane Care and Use of Laboratory Animals

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Not applicable.

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The authors declare no competing interests.

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Lian, C., Sun, J., Guan, W. et al. Circular RNA circHIPK3 Activates Macrophage NLRP3 Inflammasome and TLR4 Pathway in Gouty Arthritis via Sponging miR-561 and miR-192. Inflammation 44, 2065–2077 (2021). https://doi.org/10.1007/s10753-021-01483-2

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  • DOI: https://doi.org/10.1007/s10753-021-01483-2

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