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Transient Receptor Potential Ankyrin 1 (TRPA1) is Up-Regulated in Response to Lipopolysaccharide via P38/ Mitogen-Activated Protein Kinase (MAPK) in Dental Pulp Cells and Promotes Mineralization

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 (hDPCs) with LPS upregulated TRPA1 expression as demonstrated by RT-qPCR and western blotting. LPS stimulation also promoted nitric oxide (NO) synthesis and p38/mitogen-activated protein kinase (MAPK) phosphorylation. NOR5, an NO donor, upregulated TRPA1 expression, whereas 1400W, an inhibitor of inducible nitric oxide synthase, and SB202190, a p38/MAPK inhibitor, downregulated LPS-induced TRPA1 expression. Moreover, JT010, a TRPA1 agonist, increased the intracellular calcium concentration and extracellular signal-regulated kinase 1/2 phosphorylation, and upregulated alkaline phosphatase mRNA in hDPCs. Icilin-a TRPA1 agonist-upregulated secreted phosphoprotein 1 mRNA expression and promoted mineralized nodule formation in mouse dental papilla cells. In vivo expression 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.

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S1077 SB202190 (FHPI) SB202190 (FHPI) is a potent p38 MAPK inhibitor targeting p38α/β with IC50 of 50 nM/100 nM in cell-free assays, sometimes used instead of SB 203580 to investigate potential roles for SAPK2a/p38 in vivo. SB202190 inhibits endothelial cell apoptosis via induction of autophagy and heme oxygenase-1. SB202190 significantly suppresses Erastin‐dependent ferroptosis. (121) (3)

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