Department of Pulp Biology and Endodontics, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8549, Japan.
Department of Pediatric Dentistry, Faculty of Odonto-Stomatology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 17000, Vietnam.
Int J Mol Sci. 2024 Sep 7;25(17):9694. doi: 10.3390/ijms25179694.
MicroRNA-27a-5p (miR-27a-5p) was significantly upregulated in dental pulp inflammation, yet its underlying mechanisms remain unclear. This study investigated the effect of miR-27a-5p on the expression of proinflammatory cytokines in human dental pulp cells (hDPCs) stimulated by lipopolysaccharide (LPS). LPS-stimulated hDPCs showed concurrent increases in the expression of miR-27a-5p and proinflammatory cytokines (IL-6, IL-8, and MCP1), and the increased expression was suppressed by NF-κB inhibitor BAY 11-0785. Transfection of the miR-27a-5p mimic downregulated the expression of proinflammatory cytokines, NF-κB activity, and the expression of NF-κB signaling activators (TAB1, IRAK4, RELA, and FSTL1) in LPS-stimulated hDPCs. Luciferase reporter assays revealed that miR-27a-5p bound directly to the 3'-UTR of TAB1. siTAB1 downregulated NF-κB activity and proinflammatory cytokine expression. Downregulation of proinflammatory cytokine expression, NF-κB activity, and NF-κB signaling activator expression (TAB1, IRAK4, and RELA) was also found in LPS-stimulated rat incisor pulp tissue explants following transfection with the miR-27a-5p mimic ex vivo. MiR-27a-5p, whose expression was induced by NF-κB signaling, negatively regulated the synthesis of proinflammatory cytokines via targeting NF-κB signaling. In particular, TAB1, a potent NF-κB activator, was targeted by miR-27a-5p. These results provide insights into the negative regulatory effects of miR-27a-5p, particularly those targeting the TAB1-NF-κB signaling pathway, on pulp inflammation.
miR-27a-5p（miR-27a-5p）在牙髓炎症中显著上调，但其潜在机制尚不清楚。本研究探讨了 miR-27a-5p 对脂多糖（LPS）刺激下人牙髓细胞（hDPCs）中促炎细胞因子表达的影响。LPS 刺激的 hDPCs 显示 miR-27a-5p 和促炎细胞因子（IL-6、IL-8 和 MCP1）的表达同时增加，NF-κB 抑制剂 BAY 11-0785 抑制了这种增加。miR-27a-5p 模拟物的转染下调了 LPS 刺激的 hDPCs 中促炎细胞因子、NF-κB 活性和 NF-κB 信号激活剂（TAB1、IRAK4、RELA 和 FSTL1）的表达。荧光素酶报告基因检测显示，miR-27a-5p 直接结合到 TAB1 的 3'-UTR 上。siTAB1 下调 NF-κB 活性和促炎细胞因子表达。在 LPS 刺激的大鼠切牙牙髓组织外植体中，miR-27a-5p 模拟物的转染也发现了促炎细胞因子表达、NF-κB 活性和 NF-κB 信号激活剂（TAB1、IRAK4 和 RELA）的下调。NF-κB 信号诱导的 miR-27a-5p 通过靶向 NF-κB 信号负调控促炎细胞因子的合成。特别是，TAB1，一种有效的 NF-κB 激活剂，是 miR-27a-5p 的靶标。这些结果提供了关于 miR-27a-5p 的负调节作用的见解，特别是针对 TAB1-NF-κB 信号通路的作用，对牙髓炎症具有重要意义。
