1. Academic Validation
  2. Dual roles of TGF-β signaling in the regulation of dental epithelial cell proliferation

Dual roles of TGF-β signaling in the regulation of dental epithelial cell proliferation

  • J Mol Histol. 2021 Feb;52(1):77-86. doi: 10.1007/s10735-020-09925-1.
Hao Zhang 1 Yunyan Zhan 1 Yue Zhang 1 Guohua Yuan 1 Guobin Yang 2
Affiliations

Affiliations

  • 1 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Luoyu Road #237, Hongshan District, Wuhan, 430079, Hubei, China.
  • 2 The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & Hospital of Stomatology, Wuhan University, Luoyu Road #237, Hongshan District, Wuhan, 430079, Hubei, China. guobin.yang@whu.edu.cn.
Abstract

The purpose of this study is to investigate the molecular mechanisms and biological function of TGF-β-activated Smad1/5 in dental epithelium. Immunohistochemistry was used to detect the expressions of TGF-β signaling-related gene in mice molar germ. Primary dental epithelial cells were cultured and treated with TGF-β1 at a concentration of 0.5 or 5 ng/mL. Small molecular inhibitors, SB431542 and ML347, was used to inhibite ALK5 and ALK1/2, respectively. Small interfering RNA was used to knock down Smad1/5 or SMAD2/3. The proliferation rate of cells was evaluated by EdU assay. In the basal layer of dental epithelial bud TGF-β1 and p-Smad1/5 were highly expressed, and in the interior of the epithelial bud TGF-β1 was lowly expressed, whereas p-Smad2/3 was highly expressed. In primary cultured dental epithelial cells, low concentration of TGF-β1 activated SMAD2/3 but not Smad1/5, while high concentration of TGF-β1 was able to activate both SMAD2/3 and Smad1/5. SB431542 but not ML347 was able to block the phosphorylation of SMAD2/3 by TGF-β1. Either SB431542 or ML347 was able to block the phosphorylation of Smad1/5 by TGF-β1. EdU staining showed that high concentration of TGF-β1 promoted dental epithelial cell proliferation, which was reversed by silencing Smad1/5, whereas low concentration of TGF-β1 inhibited cell proliferation, which was reversed by silencing SMAD2/3. In conclusions, TGF-β exhibits dual roles in the regulation of dental epithelial cell proliferation through two pathways. On the one hand, TGF-β activates canonical SMAD2/3 signaling through ALK5, inhibiting the proliferation of internal dental epithelial cells. On the other hand, TGF-β activates noncanonical Smad1/5 signaling through ALK1/2-ALK5, promoting the proliferation of basal cells in the dental epithelial bud.

Keywords

Dental epithelial cell; Proliferation; Smad1/5; Smad2/3; TGF-β.

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