Transient Receptor Potential Ankyrin 1 Is Up-Regulated in Response to Lipopolysaccharide via P38/Mitogen-Activated Protein Kinase in Dental Pulp Cells and Promotes Mineralization
Transient Receptor Potential Ankyrin 1 Is Up-Regulated in Response to Lipopolysaccharide via P38/Mitogen-Activated Protein Kinase in Dental Pulp Cells and Promotes Mineralization
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牙髓细胞中瞬时受体电位锚蛋白 1 通过 P38/丝裂原激活蛋白激酶响应脂多糖而上调并促进矿化
DOI：
10.1016/j.ajpath.2020.08.016
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Okiji T
中科院分区：
文献类型：
--
作者：
Tazawa K;Kawashima N;Kuramoto M;Noda S;Fujii M;Nara K;Hashimoto K;Okiji T
在龋齿牙髓中检测到瞬时受体电位锚蛋白 1 (TRPA1) 通道表达增加，表明 TRPA1 参与外源性有害刺激后该组织的防御或修复。本研究旨在阐明牙髓细胞中脂多糖（LPS）刺激反应的诱导机制以及 TRPA1 的功能。定量 RT-PCR 和蛋白质印迹证明，用 LPS 刺激人牙髓细胞会上调 TRPA1 表达。 LPS 刺激还促进一氧化氮 (NO) 合成和 p38/丝裂原激活蛋白激酶 (MAPK) 磷酸化。 NO 供体 NOR5 上调 TRPA1 表达，而诱导型一氧化氮合酶抑制剂 1400W 和 p38/MAPK 抑制剂 SB202190 下调 LPS 诱导的 TRPA1 表达。此外，TRPA1 激动剂 JT010 增加了人牙髓细胞中的细胞内钙浓度和细胞外信号调节激酶 1/2 磷酸化，并上调碱性磷酸酶 mRNA。 Icilin（一种 TRPA1 激动剂）可上调分泌型磷蛋白 1 mRNA 表达，并促进小鼠牙乳头细胞中矿化结节的形成。在沿龋齿第三级牙本质的成牙本质细胞中检测到 TRPA1 的体内表达。总之，本研究证明 LPS 刺激通过 NO-p38 MAPK 信号通路诱导 TRPA1，TRPA1 激动剂促进牙髓细胞的分化或矿化。
Increased expression of the transient receptor potential ankyrin 1 (TRPA1) channel has been detected in carious tooth pulp, suggesting involvement of TRPA1 in defense or repair of this tissue after exogenous noxious stimuli. This study aimed to elucidate the induction mechanism in response to lipopolysaccharide (LPS) stimulation and the function of TRPA1 in dental pulp cells. Stimulation of human dental pulp cells with LPS up-regulated TRPA1 expression, as demonstrated by quantitative RT-PCR and Western blotting. LPS stimulation also promoted nitric oxide (NO) synthesis and p38/mitogen-activated protein kinase (MAPK) phosphorylation. NOR5, an NO donor, up-regulated TRPA1 expression, whereas 1400W, an inhibitor of inducible nitric oxide synthase, and SB202190, a p38/MAPK inhibitor, down-regulated LPS-induced TRPA1 expression. Moreover, JT010, a TRPA1 agonist, increased the intracellular calcium concentration and extracellular signal-regulated kinase 1/2 phosphorylation, and up-regulated alkaline phosphatase mRNA in human dental pulp cells. Icilin—a TRPA1 agonist—up-regulated secreted phosphoprotein 1 mRNA expression and promoted mineralized nodule formation in mouse dental papilla cells.In vivoexpression of TRPA1 was detected in odontoblasts along the tertiary dentin of carious teeth. In conclusion, this study demonstrated that LPS stimulation induced TRPA1 via the NO-p38 MAPK signaling pathway and TRPA1 agonists promoted differentiation or mineralization of dental pulp cells.