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MiR-200b is involved in Tgf-β signaling to regulate mammalian palate development.

Title
MiR-200b is involved in Tgf-β signaling to regulate mammalian palate development.
Authors
Sungwook Kwak;Hyuk-Jae Kwon;Kyoung-Won Cho;Jong-Min Lee;Jeong-Oh Shin;Min-Jung Lee;Sung-Won Cho;Kye-Seong Kim;Han-Sung Jung
Issue Date
2012
Journal Title
Histochemistry and Cell Biology
ISSN
0948-6143
Citation
Histochemistry and Cell Biology, Vol.137(1) : 67~78, 2012
Abstract
Various cellular and molecular events are involved in palatogenesis, including apoptosis, epithelial-mesenchymal transition (EMT), cell proliferation, and cell migration. Smad2 and Snail, which are well-known key mediators of the transforming growth factor beta (Tgf-β) pathway, play a crucial role in the regulation of palate development. Regulatory effects of microRNA 200b (miR-200b) on Smad2 and Snail in palatogenesis have not yet been elucidated. The aim of this study is to determine the relationship between palate development regulators miR-200b and Tgf-β-mediated genes. Expression of miR-200b, E-cadherin, Smad2, and Snail was detected in the mesenchyme of the mouse palate, while miR-200b was expressed in the medial edge epithelium (MEE) and palatal mesenchyme. After the contact of palatal shelves, miR-200b was no longer expressed in the mesenchyme around the fusion region. The binding activity of miR-200b to both Smad2 and Snail was examined using a luciferase assay. MiR-200b directly targeted Smad2 and Snail at both cellular and molecular levels. The function of miR-200b was determined by overexpression via a lentiviral vector in the palatal shelves. Ectopic expression of miR-200b resulted in suppression of these Tgf-β-mediated regulators and changes of apoptosis and cell proliferation in the palatal fusion region. These results suggest that miR-200b plays a crucial role in regulating the Smad2, Snail, and in apoptosis during palatogenesis by acting as a direct non-coding, influencing factor. Furthermore, the molecular interactions between miR-200b and Tgf-β signaling are important for proper palatogenesis and especially for palate fusion. Elucidating the mechanism of palatogenesis may aid the design of effective gene-based therapies for the treatment of congenital cleft palate.
URI
http://link.springer.com/article/10.1007%2Fs00418-011-0876-1

http://ir.ymlib.yonsei.ac.kr/handle/22282913/90369
DOI
10.1007/s00418-011-0876-1
Appears in Collections:
1. 연구논문 > 2. College of Dentistry > Dept. of Oral Biology
Yonsei Authors
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