Antagonistic Effects of Smad2 Versus Smad7 are Sensitive to Their Expression Level during Tooth Development

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Abstract

Members of the transforming growth factor-β (TGF-β) superfamily regulate cell proliferation, differentiation, and apoptosis, controlling the development and maintenance of most tissues. TGF-β signal is transmitted through the phosphorylation of Smad proteins by TGF-β receptor serine/threonine kinase. During early tooth development, TGF-β inhibits proliferation of enamel organ epithelial cells but the underlying molecular mechanisms are largely unknown. Here we tested the hypothesis that antagonistic effects between Smad2 and Smad7 regulate TGF-β signaling during tooth development. Attenuation of Smad2 gene expression resulted in significant advancement of embryonic tooth development with increased proliferation of enamel organ epithelial cells, while attenuation of Smad7 resulted in significant inhibition of embryonic tooth development with increased apoptotic activity within enamel organ epithelium. These findings suggest that different Smads may have differential activities in regulating TGF-β-mediated cell proliferation and death. Furthermore, functional haploinsufficiency of Smad2, but not Smad3, altered TGF-β-mediated tooth development. The results indicate that Smads are critical factors in orchestrating TGF-β-mediated gene regulation during embryonic tooth development. The effectiveness of TGF-β signaling is highly sensitive to the level of Smad gene expression.

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Ito, Y., Zhao, J., Mogharei, A., Shuler, C. F., Weinstein, M., Deng, C., & Chai, Y. (2001). Antagonistic Effects of Smad2 Versus Smad7 are Sensitive to Their Expression Level during Tooth Development. Journal of Biological Chemistry, 276(47), 44163–44172. https://doi.org/10.1074/jbc.M011424200

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