Response of TGF-β isoforms in epithelial-mesenchymal transition of enamel epithelial cells. (November 2022)

• Record Type: Journal Article
• Authors: Miyakawa, Yuri; Chiba-Ohkuma, Risako; Karakida, Takeo; Yamamoto, Ryuji; Kobayashi, Saeko; Yamakoshi, Yasuo; Asada, Yoshinobu
• Is Part Of: Archives of oral biology. Volume 143(2022)
• Publication Date: 2022-11
• Subjects: EMT epithelial-mesenchymal transition -- NGS; next-generation sequencing -- HRP horse radish peroxidase -- qPCR quantitative polymerase chain reaction -- Smad3 mothers against decapentaplegic homolog 3 -- PAI-1 plasminogen activator inhibitor-1 -- GAPDH glyceraldehyde-3-phosphate dehydrogenase -- α-SMA alpha smooth muscle actin -- HERS Hertwig's epithelial root sheath; Epithelial-mesenchymal transition -- Growth factor -- Cell biology -- Signal transduction -- Enamel formation -- Cell differentiation; Mouth -- Periodicals; Mouth -- Diseases -- Periodicals; Dentistry -- Periodicals; Electronic journals; 617.6005
• DOI: 10.1016/j.archoralbio.2022.105540
• Languages: English
• ISSNs: 0003-9969

Abstract

Abstract: Objective: During enamel formation, transforming growth factor-beta (TGF-β) isoforms exhibit different activities for gene expression, apoptosis, and endocytosis. This study aimed to investigate the differential response of TGF-β isoforms to epithelial-mesenchymal transition (EMT) in enamel epithelial cells. Design: Using a mouse enamel epithelial cell line (mHAT9d) cultured in the presence of each TGF-β isoform, (1) the morphological changes in EMT were explored, (2) EMT-related genes were analyzed by next-generation sequencing (NGS), (3) TGF-β pathway for EMT was identified by inhibition experiments, and (4) the expression of the TGF-β receptor gene in response to the binding affinity of the TGF-β isoform were analyzed. Results: EMT was observed in mHAT9d cultured in the presence of TGF-β1 and β3 but not TGF-β2. The expression of both epithelial and mesenchymal marker genes was observed in mHAT9d exhibiting EMT. NGS analysis suggested extracellular signal-regulated kinase (ERK) and Rho pathways as TGF-β signaling pathways associated with EMT. However, EMT in mHAT9d cultured in the presence of TGF-β1 or β3 occurred even in presence of an ERK1/2 inhibitor and was suppressed by Rho-kinase inhibitor. The expression of co-receptors for TGF-β signaling in mHAT9d cells reduced following stimulation with each TGF-β isoform. In contrast, endoglin levels increased following TGF-β1 or β3 stimulation, but no change was noted in response to TGF-β2. Conclusions: We propose that in TGF-β-stimulated enamel epithelial cells, EMT mainly occurred via the Rho signaling pathway, and the differences in response across TGF-β isoforms were due to their endoglin-mediated binding affinity for the TGF-β receptor. Graphical Abstract: ga1 Highlights: TGF-β isoforms exhibits different reactivity for EMT of enamel epithelial cells. EMT by TGF-β stimulation mainly occurs via Rho signaling pathway. Binding affinity for endoglin causes the different response for TGF-β isoforms.