Mediator1 involved in functional integration of Smad3 and Notch1 promoting enamel mineralization.

Autor: Wei R; School of Stomatology, Tianjin Medical University, Tianjin, 300014, China. Electronic address: weiranvalerie@126.com., Guo S; School of Stomatology, Tianjin Medical University, Tianjin, 300014, China. Electronic address: shulingguo@tmu.edu.cn., Meng Z; School of Stomatology, Tianjin Medical University, Tianjin, 300014, China. Electronic address: ddsmzs@sina.com., Li Z; School of Stomatology, Tianjin Medical University, Tianjin, 300014, China. Electronic address: 15810746648@163.com., Liu J; School of Stomatology, Tianjin Medical University, Tianjin, 300014, China. Electronic address: liujiachengboy@126.com., Hu L; Immunology Department, Key Laboratory of Immune Microenvironment and Disease, Ministry of Education, Tianjin Medical University, Tianjin, 300014, China. Electronic address: lizhihu@tmu.edu.cn., Sui L; School of Stomatology, Tianjin Medical University, Tianjin, 300014, China. Electronic address: suilei@tmu.edu.cn.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2023 Jun 30; Vol. 663, pp. 47-53. Date of Electronic Publication: 2023 Apr 18.
DOI: 10.1016/j.bbrc.2023.04.053
Abstrakt: Enamel hypoplasia is a tooth development defection due to the disruption of enamel matrix mineralization, manifesting as chalky white phenotype. Multiple genes may be involved in this tooth agenesis. It has been proved that ablation of coactivator Mediator1 (Med1) switches the cell fate of dental epithelia, resulting in abnormal tooth development via Notch1 signaling. Smad3 (-/-) mice displays the similar chalky white incisors. However, the expression of Smad3 in Med1 ablation mice and the impact of Med1 on functional integration between Smad3 and Notch1 remains unclear. Cre-loxP-based C57/BL6 mice with epithelial-specific Med1 knockout (Med1 KO) backgrounds were generated. Mandibles and dental epithelial stem cells (DE-SCs) from incisors cervical loop (CL) were isolated from wild-type (CON) mice and Med1 KO mice. Transcriptome sequencing was used to analyze the differences of CL tissue between KO and CON mice. The results revealed the enrichment of TGF-β signaling pathway. qRT-PCR and western blot were performed to show the gene and protein expression of Smad3, pSmad3, Notch1 and NICD, the key regulators of TGF-β and Notch1 signaling pathway. Expression of Notch1 and Smad3 was confirmed to be down-regulated in Med1 KO cells. Using activators of Smad3 and Notch1 on Med1 KO cells, both pSmad3 and NICD were rescued. Moreover, adding inhibitors and activators of Smad3 and Notch1 to cells of CON groups respectively, the protein expressions of Smad3, pSmad3, Notch1 and NICD were synergistically affected. In summary, Med1 participates in the functional integration of Smad3 and Notch1, thus promoting enamel mineralization.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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