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miR-496/MMP10 Is Involved in the Proliferation of IL-1β-Induced Fibroblast-Like Synoviocytes Via Mediating the NF-κB Signaling Pathway

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Abstract

Rheumatoid arthritis (RA) is a common chronic autoimmune disease featured by synovial inflammation. miR-496 is closely involved in various pathologic conditions. However, its role in RA has not yet been elucidated. Expression of miR-496 and MMP10 was determined based on the clinical samples with RA retrieved from the Gene Expression Omnibus (GEO) datasets. In vitro model of RA was constructed in MH7A cells stimulated by IL-1β (10 ng/mL). Cell counting kit 8 (CCK-8) and flow cytometry experiments were implemented to investigate the cell viability and apoptosis rate of MH7A cells. TargetScan was applied to identify the targets of miR-496, and the regulation of miR-496 on MMP10 expression was validated by a dual-luciferase reporter gene assay. qRT-PCR and western blot analyses were conducted to examine the expression. miR-496 expression was decreased in RA tissues and MH7A cells after IL-1β treatment. Overexpression of miR-496 significantly inhibited IL-1β-treated MH7A cell viability. MMP10 was identified as a target of miR-496 and its expression was negatively regulated by miR-496. The effects of miR-496 on MH7A cell proliferation and apoptosis were reversed by MMP10. The activity of NF-κB pathway was associated with the miR-496/MMP10 axis in IL-1β-stimulated MH7A cells. To summarize, this study demonstrated that miR-496 can impair the proliferative ability and facilitate the apoptosis of IL-1β-treated MH7A through regulating MMP10 expression and NF-κB signaling pathway.

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Data Availability

The datasets supporting the conclusions of this article are included within the article.

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Funding

This study was supported by Science and Technology talent cultivation Project of Tianjin Health Commission (No. RC20156), and Science and Technology Fund of Tianjin First Central Hospital (No. 2020CM10).

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Authors and Affiliations

  1. Department of Orthopedics, Tianjin First Central Hospital, No.24 FuKang Road, Nankai District, Tianjin, 300192, China

    Xue-Wu Xing & Shu-Xin Feng

  2. Department of Orthopedics, Tianjin Medical University General Hospital, No.154 Anshan Road, Heping District, Tianjin, 300052, China

    Hong-Yu Shi, Shen Liu & Shi-Qing Feng

  3. Department of Rheumatology, Tianjin First Central Hospital, No.24 FuKang Road, Nankai District, Tianjin, 300192, China

    Bao-Qi Gong

Authors
  1. Xue-Wu Xing
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  2. Hong-Yu Shi
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Contributions

Shi-Qing Feng, Bao-Qi Gong and Xue-Wu Xing conceived and designed the present study, and contributed to writing the manuscript. Hong-Yu Shi and Shen Liu analyzed experimental data. Xue-Wu Xing, Hong-Yu Shi, Shen Liu and Shu-Xin Feng performed the experiments. All authors read and approved the final manuscript.

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Correspondence to Shi-Qing Feng or Bao-Qi Gong.

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Xing, XW., Shi, HY., Liu, S. et al. miR-496/MMP10 Is Involved in the Proliferation of IL-1β-Induced Fibroblast-Like Synoviocytes Via Mediating the NF-κB Signaling Pathway. Inflammation 44, 1359–1369 (2021). https://doi.org/10.1007/s10753-021-01421-2

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