Upregulated LncRNA-Meg3 modulates the proliferation and survival of MEPM cells via interacting with Smad signaling in TCDD-induced cleft palate.
Cleft palate
MEPM
Meg3
Smad signaling
TCDD
Journal
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
ISSN: 1873-6351
Titre abrégé: Food Chem Toxicol
Pays: England
ID NLM: 8207483
Informations de publication
Date de publication:
19 Dec 2023
19 Dec 2023
Historique:
received:
05
05
2023
revised:
11
12
2023
accepted:
18
12
2023
medline:
22
12
2023
pubmed:
22
12
2023
entrez:
21
12
2023
Statut:
aheadofprint
Résumé
Exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in utero can result in high rates of cleft palate (CP) formation, yet the underlying mechanisms remain to be characterized. In vivo, the lncRNA Meg3 was upregulated following TCDD treatment in CP-associated murine embryonic palatal tissue, with concomitant changes in proliferative and apoptotic activity in these murine embryonic palatal mesenchymal (MEPM) cells. Meg3 can modulate the TGF-β/Smad to control the proliferation, survival, and differentiation of cells. Accordingly, TCCD and TGF-β1 were herein used to treat MEPM cells in vitro, revealing that while TCDD exposure altered the proliferative activity and apoptotic death of these cells, exogenous TGF-β1 exposure antagonized these effects via TGF-β/Smad signaling. TCDD promoted Meg3 upregulation, whereas TGF-β1 suppressed TCDD-driven upregulation of this lncRNA. Meg3 was additionally determined to directly interact with Smad2, with significant Meg3 enrichment in Smad2-immunoprecipitates following TCDD treatment. When Meg3 was silenced, the impact of TCDD on Smad signaling, proliferative activity, and apoptosis were ablated, while the effects of exogenous TGF-β1 were unchanged. This supports a model wherein Meg3 is upregulated in TCDD-exposed palatal tissue whereupon it can interact with Smad2 to suppress Smad-dependent signaling, thus controlling MEPM cell proliferation and apoptosis, contributing to TCDD-induced CP, which provides a theoretical support for the precautions of cleft palate induced by TCDD.
Identifiants
pubmed: 38128685
pii: S0278-6915(23)00813-X
doi: 10.1016/j.fct.2023.114410
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
114410Informations de copyright
Copyright © 2023. Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and the manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed.