RRC ID 54759
Author Nakayama Y, Tsuruya Y, Noda K, Yamazaki-Takai M, Iwai Y, Ganss B, Ogata Y.
Title Negative feedback by SNAI2 regulates TGFβ1-induced amelotin gene transcription in epithelial-mesenchymal transition.
Journal J Cell Physiol
Abstract Junctional epithelium (JE) demonstrates biological responses with the rapid turnover of gingival epithelial cells. The state occurs in inflammation of gingiva and wound healing after periodontal therapy. To understand the underlying mechanisms and to maintain homeostasis of JE, it is important to investigate roles of JE-specific genes. Amelotin (AMTN) is localized at JE and regulated by inflammatory cytokines and apoptotic factors that represent a critical role of AMTN in stabilizing the dentogingival attachment, which is an entrance of oral bacteria. In this study, we demonstrated that the AMTN gene expression was regulated by SNAI2 and transforming growth factor β1 (TGFβ1)-induced epithelial-mesenchymal transition (EMT) that occurs in wound healing and fibrosis during chronic inflammation. SNAI2 downregulated AMTN gene expression via SNAI2 bindings to E-boxes (E2 and E4) in the mouse AMTN gene promoter in EMT of gingival epithelial cells. Meanwhile, TGFβ1-induced AMTN gene expression was attenuated by SNAI2 and TGFβ1-induced SNAI2, without inhibition of the TGFβ1-Smad3 signaling pathway. Moreover, SNAI2 small interfering RNA (siRNA) rescued SNAI2-induced downregulation of AMTN gene expression, and TGFβ1-induced AMTN gene expression was potentiated by SNAI2 siRNA. Taken together, these data demonstrated that AMTN gene expression in the promotion of EMT was downregulated by SNAI2. The inhibitory effect of AMTN gene expression was an independent feedback on the TGFβ1-Smad3 signaling pathway, suggesting that the mechanism can be engaged in maintaining homeostasis of gingival epithelial cells at JE and the wound healing phase.
Volume 234(7)
Pages 11474-11489
Published 2019-7-1
DOI 10.1002/jcp.27804
PMID 30488439
MeSH Animals Cell Line Dental Enamel Proteins / genetics Dental Enamel Proteins / metabolism* Down-Regulation Epithelial Cells / metabolism* Epithelial-Mesenchymal Transition / physiology* Gene Expression Regulation / drug effects Gingiva / cytology Mice Snail Family Transcription Factors / genetics Snail Family Transcription Factors / metabolism* Transfection Transforming Growth Factor beta1 / pharmacology*
IF 4.522
Times Cited 1
Human and Animal Cells GE1(RCB1709)