MAP kinase phosphatase MKP-1 regulates p-ERK1/2 signaling pathway with fluoride treatment
| Autor: | Tao Xi, Jiali Su, Kristina Xiao Liang, Sijia Liu, Yang Li, Lin Zhao, Jianping Ruan, Ruizhe Huang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Biophysics Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine stomatognathic system Sodium fluoride medicine Molecular Biology biology Chemistry Cell Biology Tooth enamel medicine.disease Cell biology stomatognathic diseases 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Mitogen-activated protein kinase MAP kinase phosphatase biology.protein Ameloblast Fluoride Dental fluorosis |
| Zdroj: | Biochemical and Biophysical Research Communications-BBRC |
| ISSN: | 1090-2104 |
| Popis: | Background Dental fluorosis is characterized by hypomineralization of tooth enamel caused by ingestion of excessive fluoride during enamel formation. Excess fluoride could have effects on the ERK signaling, which is essential for the ameloblasts differentiation and tooth development. MAP kinase phosphatase-1 (MKP-1) plays a critical role in regulating ERK related kinases. However, the role of MKP-1 in ameloblast and the mechanisms of MKP-1/ERK signaling in the pathogenesis of dental fluorosis are incompletely understood. Results Here, we adopted an in vitro fluorosis cell model using murine ameloblasts-like LS8 cells by employing sodium fluoride (NaF) as inducer. Using this system, we demonstrated that fluoride exposure led to an inhibition of p- MEK and p-ERK1/2 with a subsequent increase in MKP-1 expression in a dose-dependent manner. We further identified, under high dose fluoride, MKP-1 acted as a negative regulator of the fluoride-induced p-ERK1/2 signaling, leading to downregulation of CREB, c-myc, and Elk-1. Conclusion Our results identify a novel MKP-1/ERK signaling mechanism that regulates dental fluorosis and provide a framework for studying the molecular mechanisms of intervention and fluorosis remodeling under normal and pathological conditions. MKP-1 inhibitors may prove to be a benefit therapeutic strategy for dental fluorosis treatment. |
| Databáze: | OpenAIRE |
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