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Retinoic acid receptor beta mediates all-trans retinoic acid facilitation of mesenchymal stem cells neuronal differentiation.
MedLine Citation:
PMID:  23318218     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
All-trans retinoic acid plays an important role in nervous system development. However, the effects of all-trans retinoic acid on the neuronal differentiation of mesenchymal stem cells and the mechanisms through which this differentiation takes place are still poorly understood. Here, we investigated the biological effects of all-trans retinoic acid on the neuronal differentiation of mesenchymal stem cells and the signaling pathways that mediated these effects. We found that the neuronal differentiation efficiency of mesenchymal stem cells following all-trans retinoic acid pre-induction was greater and the axonal length was longer than was observed with mesenchymal stem cells that were not pre-induced. mRNA and protein levels of the neural-markers Nestin, NSE, MAP-2, Tau and Tuj1 were stronger in neural-like cells derived from all-trans retinoic acid-pretreated mesenchymal stem cells than in those not pre-induction. Interestingly, the neuronal excitability of differentiated neural-like cells exhibited the same patterns between these two groups. Clear expression of retinoic acid receptor alpha and gamma in mesenchymal stem cells was observed, while retinoic acid receptor beta was barely detected. However, retinoic acid receptor beta expression in mesenchymal stem cells after neuronal induction increased dramatically, in contrast with retinoic acid receptor alpha and gamma expression, and retinoic acid receptor beta expression in mesenchymal stem cells receiving all-trans retinoic acid pre-induction was even stronger. Next, retinoic acid receptor alpha, beta and gamma were over-expressed by recombinant adenovirus infection prior to neuronal induction. Retinoic acid receptor alpha and gamma over-expression did not impact the neuronal differentiation of mesenchymal stem cells. However, retinoic acid receptor beta over-expression promoted neuronal differentiation to a similar level as observed following all-trans retinoic acid pre-induction. The neuronal differentiation promoting effects of all-trans retinoic acid on mesenchymal stem cells could be inhibited by siRNA silencing of retinoic acid receptor beta and by LE135, an inhibitor of retinoic acid receptor beta. Taken together, these results suggest that all-trans retinoic acid pre-induction facilitates the neuronal differentiation of mesenchymal stem cells. These facilitation effects are achieved by activating the retinoic acid receptor β signaling pathway.
Authors:
Min Gong; Yang Bi; Wei Jiang; Yun Zhang; Li Chen; Nali Hou; Jie Chen; Tingyu Li
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-11
Journal Detail:
Title:  The international journal of biochemistry & cell biology     Volume:  -     ISSN:  1878-5875     ISO Abbreviation:  Int. J. Biochem. Cell Biol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9508482     Medline TA:  Int J Biochem Cell Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013. Published by Elsevier Ltd.
Affiliation:
Children's Nutrition Research Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, China; Ministry of Education Key Laboratory of Child Development and Disorders; Key Laboratory of Pediatrics in Chongqing; Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Chongqing 400014, China.
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