Transforming growth factor-beta1 up-regulates the expression of nerve growth factor through mitogen-activated protein kinase signaling pathways in dental pulp cells.
Transforming growth factor-beta1 (TGF-beta1) and nerve growth factor (NGF) have been detected in pulp tissues after injury and are implicated in the differentiation of odontoblast-like cells and in pulp tissue repair. We examined TGF-beta1-mediated regulation of NGF and investigated its signaling pathways in human dental pulp cells. Analyses by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) revealed that TGF-beta1 (1 ng ml(-1)) induced NGF mRNA and protein expression through the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Blockade of the p38 MAPK and JNK pathways with the respective upstream inhibitors (SB203580 and SP600125) abolished the TGF-beta1-mediated induction of NGF. In addition, SB225002, a G-protein-coupled receptor antagonist, and staurosporine, a serine-threonine kinase inhibitor, partially inhibited TGF-beta1-mediated induction of NGF. Phospho-p38 MAPK was suppressed by SB225002, whereas phospho-JNK was inhibited by staurosporine. We conclude that TGF-beta1 up-regulates NGF in human dental pulp cells. This suggests that TGF-beta1 plays a role in NGF regulation during pulp tissue repair. The signal of TGF-beta1 involves the activation of MAPK, especially p38 and JNK. We suggest that crosstalk between TGF-beta1 and G-protein-coupled receptor signaling also participates in the inductive mechanism.
Yongchaitrakul
Tussanee
T
Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Pavasant
Prasit
P
D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020932:Nerve Growth Factor / Q000096:biosynthesis*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D015854:Up-Regulation
D053773:Transforming Growth Factor beta1; D020932:Nerve Growth Factor; D020928:Mitogen-Activated Protein Kinases