Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Army Medical University, Chongqing, China.
Urology, Southwest Hospital, Army Medical University, Chongqing, China.
Int J Rheum Dis. 2023 Apr;26(4):699-709. doi: 10.1111/1756-185X.14622. Epub 2023 Feb 26.
Dual-specificity phosphatase 5 (DUSP5) is a novel anti-inflammatory modulator in many inflammatory diseases. However, the role of DUSP5 in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) remains unknown. In this study, we aimed to explore the biological function and regulation of DUSP5 in FLS. We found that lower DUSP5 expression level was detected in collagen-induced arthritis (CIA) and synoviocyte MH7A. Overexpression of DUSP5 markedly decreased the proliferation, migration, and invasion of MH7A, which correlated with suppressing the phosphorylation of extracellular signal-regulated kinase (ERK). Moreover, DUSP5 was identified as a novel target gene of miR-216a-3p, which was upregulated in FLS. Therefore, DUSP5 expression was negatively regulated by miR-216a-3p, and the effect of DUSP5 overexpression on FLS was reversed by miR-216a-3p mimics. Overall, our study demonstrates that DUSP5 is a miR-216a-3p target gene and its anti-inflammatory function in FLS via inactivation of ERK. These results revealed that the miR-216a-3p/DUSP5 pathway may play a crucial role in the malignant behavior of FLS, which may serve as a new target for the treatment of RA.
双特异性磷酸酶 5（DUSP5）是许多炎症性疾病中一种新型的抗炎调节剂。然而，DUSP5 在类风湿关节炎（RA）成纤维样滑膜细胞（FLS）中的作用尚不清楚。在本研究中，我们旨在探索 DUSP5 在 FLS 中的生物学功能和调节作用。我们发现，在胶原诱导性关节炎（CIA）和滑膜细胞 MH7A 中，DUSP5 的表达水平较低。DUSP5 的过表达显著降低了 MH7A 的增殖、迁移和侵袭能力，这与细胞外信号调节激酶（ERK）的磷酸化抑制有关。此外，DUSP5 被鉴定为 miR-216a-3p 的一个新的靶基因，该基因在 FLS 中上调。因此，DUSP5 的表达受 miR-216a-3p 的负调控，而过表达 DUSP5 的作用可被 miR-216a-3p 模拟物逆转。总之，我们的研究表明，DUSP5 是 miR-216a-3p 的靶基因，通过 ERK 失活发挥其在 FLS 中的抗炎功能。这些结果表明，miR-216a-3p/DUSP5 通路可能在 FLS 的恶性行为中发挥关键作用，可作为治疗 RA 的新靶点。
