Identification of Smad-dependent and -independent signaling with transforming growth factor-β type 1/2 receptor inhibition in palatogenesis
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 wi...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2020-04-01
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| Series: | Journal of Oral Biology and Craniofacial Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212426820300026 |
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| Summary: | 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. |
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| ISSN: | 2212-4268 |