Identification of Smad-dependent and -independent signaling with transforming growth factor-β type 1/2 receptor inhibition in palatogenesis
© 2020 Craniofacial Research Foundation. Published by Elsevier B.V. All rights reserved..
TGF-β signaling is one of important function during palatal fusion. Three types of TGF-β receptor (TβR1, TβR2, and TβR3) have been identified, and play essential roles in mechanisms leading to palatal fusion. However, the balance between Smad-dependent/-independent signaling during palatal fusion with inhibited TβR1/2 functions is not fully understood. The objective of this study was to investigate palatal fusion via TGF-β signaling when TβR1 and TβR2, but not TβR3, were inhibited. In addition, the present study examined the functional balance between Smad-dependent/-independent signaling and related gene expression. Palatal organ cultures were treated with TβR1/2 inhibitor in vitro. Control palates were cultured without inhibitor. We observed histological phenotype of palatal fusion, and evaluation of expression pattern by Western blot or real time RT-PCR. Palatal organ cultures treated with the inhibitor did not fuse and the medial edge epithelium remained at embryonic 13 day +72 h in culture. The inhibitor decreased TβR1 and TβR2 expression by approximately 90%, but did not affect TβR3 expression. The expression of p-Smad2 and p-Smad3 was significantly decreased in treated palates compared with controls. The expression of p-Smad4 was slightly decreased in treated palates compared with controls. Smad-independent signaling was also affected by the inhibitor; p-ERK, p-JNK, and p-p38 expressions was significantly reduced in treated palates compared with controls. The expression of transcription factors (Runx1 and Msx1) and extracellular matrix proteins (MMP2/13) was also significantly decreased by inhibitor exposure. Treatment with TβR1/2 inhibitor altered the patterns of the Smad-dependent and -independent signaling pathways during palatal fusion.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Journal of oral biology and craniofacial research - 10(2020), 2 vom: 13. Apr., Seite 43-48 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Suzuki, Yoshimi [VerfasserIn] |
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| Links: |
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| Themen: |
Cleft palate |
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| Anmerkungen: |
Date Revised 28.09.2020 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.jobcr.2020.01.002 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM306828464 |
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| 520 | |a © 2020 Craniofacial Research Foundation. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a TGF-β signaling is one of important function during palatal fusion. Three types of TGF-β receptor (TβR1, TβR2, and TβR3) have been identified, and play essential roles in mechanisms leading to palatal fusion. However, the balance between Smad-dependent/-independent signaling during palatal fusion with inhibited TβR1/2 functions is not fully understood. The objective of this study was to investigate palatal fusion via TGF-β signaling when TβR1 and TβR2, but not TβR3, were inhibited. In addition, the present study examined the functional balance between Smad-dependent/-independent signaling and related gene expression. Palatal organ cultures were treated with TβR1/2 inhibitor in vitro. Control palates were cultured without inhibitor. We observed histological phenotype of palatal fusion, and evaluation of expression pattern by Western blot or real time RT-PCR. Palatal organ cultures treated with the inhibitor did not fuse and the medial edge epithelium remained at embryonic 13 day +72 h in culture. The inhibitor decreased TβR1 and TβR2 expression by approximately 90%, but did not affect TβR3 expression. The expression of p-Smad2 and p-Smad3 was significantly decreased in treated palates compared with controls. The expression of p-Smad4 was slightly decreased in treated palates compared with controls. Smad-independent signaling was also affected by the inhibitor; p-ERK, p-JNK, and p-p38 expressions was significantly reduced in treated palates compared with controls. The expression of transcription factors (Runx1 and Msx1) and extracellular matrix proteins (MMP2/13) was also significantly decreased by inhibitor exposure. Treatment with TβR1/2 inhibitor altered the patterns of the Smad-dependent and -independent signaling pathways during palatal fusion | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Cleft palate | |
| 650 | 4 | |a Medial edge epithelial cell | |
| 650 | 4 | |a Palatal fusion | |
| 650 | 4 | |a Smad-dependent/-independent | |
| 650 | 4 | |a TGF-β signaling | |
| 700 | 1 | |a Nakajima, Akira |e verfasserin |4 aut | |
| 700 | 1 | |a Kawato, Takayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Iwata, Koichi |e verfasserin |4 aut | |
| 700 | 1 | |a Motoyoshi, Mitsuru |e verfasserin |4 aut | |
| 700 | 1 | |a Shuler, Charles F |e verfasserin |4 aut | |
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