LncRNA Meg3-mediated regulation of the Smad pathway in atRA-induced cleft palate
| Autor: | Ning Li, Xiaozhuan Liu, Haodi Yue, Zhidong He, Tingting Zhang, Xiuli Zhang, Yuwei Zhang, Zengli Yu, Suhua Gao, Yao Chen, Zhitao Li, Lijun Shen |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Retinoic acid Smad Proteins Tretinoin SMAD Toxicology 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Keratolytic Agents Downregulation and upregulation Pregnancy Mesenchymal cell proliferation Animals MEG3 Cell growth Chemistry Palate Gene Expression Regulation Developmental General Medicine Cell biology Cleft Palate 030104 developmental biology Female RNA Long Noncoding Smad2 Protein Secondary palate 030217 neurology & neurosurgery |
| Zdroj: | Toxicology letters. 341 |
| ISSN: | 1879-3169 |
| Popis: | Palatal mesenchymal cell proliferation is essential to the process of palatogenesis, and the proliferation of mouse embryonic palate mesenchymal (MEPM) cells is impacted by both all-trans retinoic acid (atRA) and the TGF-β/Smad signaling pathway. The long non-coding RNA (lncRNA) MEG3 has been shown to activate TGF-β/Smad signaling and to thereby regulate cell proliferation, differentiation, and related processes. Herein, we found that atRA treatment (100 mg/kg) promoted Meg3 upregulation in MEPM cells, and that such upregulation was linked to the suppression of MEPM cell proliferation in the context of secondary palate fusion on gestational day (GD) 13 and 14. Moreover, the demethylation of specific CpG sites within the lncRNA Meg3 promoter was detected in atRA-treated MEPM cells, likely explaining the observed upregulation of this lncRNA. Smad signaling was also suppressed by atRA treatment in these cells, and RNA immunoprecipitation analyses revealed that Smad2 can directly interact with Meg3 in MEPM cells following atRA treatment. Therefore, we propose a model wherein Meg3 is involved in the suppression of MEPM cell proliferation, functioning at least in part via interacting with the Smad2 protein and thereby suppressing Smad signaling in the context of atRA-induced cleft palate. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect