Document Detail

Retinoic acid regulates gap junction intercellular communication in human endometrial stromal cells through modulation of the phosphorylation status of connexin 43.
MedLine Citation:
PMID:  23042455     Owner:  NLM     Status:  MEDLINE    
Previous studies revealed that gap junction intercellular communication (GJIC) among uterine stromal cells plays critical roles in modulating decidualization, neovasularization, and embryo implantation. Connexin (Cx) proteins are the major component of gap junctions and Cx43 is the most widely expressed connexin in endometrium. Phosphorylation of Cx43 was found to impair gap junction communication in this tissue. Using primary human endometrial stromal cells (ESCs) and a stable high telomerase-expressing ESC transfectant (T-HESC), we found that retinoic acid (RA) altered the phosphorylation status of Cx43 protein such that there was a decrease in the phosphorylated (P1 and P2) species accompanied by an increase in the non-phosphorylated (P0) form. This process is dependent on protein phosphatase 2A (PP2A) activity since selective PP2A inhibitors prevented the ability of RA to dephosphorylate Cx43. Although RA had no effect on total PP2A expression or activity, it significantly increased the intracellular association of Cx43 and PP2A. Inhibition of transcription and protein synthesis by actinomycin D and cycloheximide, respectively, had no effect on the RA-induced changes in the Cx43 phosphorylation pattern. Furthermore, BMS493, a potent antagonist of the classical RA-mediated transcriptional pathway, did not inhibit RA-induced Cx43 dephosphorylation. Our data indicate that RA stimulates physical association of PP2A with Cx43, resulting in the dephosphorylation of Cx43 and, as a consequence, up-regulation of GJIC in ESCs. This process is independent of new mRNA and protein synthesis and suggests a novel mechanism by which aberrant retinoid metabolism can explain certain reproductive disorders manifested by dysfunctional endometrial cell GJIC.
Juanjuan Wu; Robert N Taylor; Neil Sidell
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  228     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-01-02     Completed Date:  2013-05-22     Revised Date:  2013-06-18    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  903-10     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Division of Research, Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
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MeSH Terms
Cell Communication / drug effects*,  genetics
Cells, Cultured
Connexin 43 / genetics,  metabolism*
Cycloheximide / pharmacology
Dactinomycin / pharmacology
Endometrium / drug effects*,  metabolism
Gap Junctions / drug effects*,  genetics,  metabolism
Phosphorylation / drug effects
Protein Phosphatase 2 / genetics,  metabolism
RNA, Messenger / genetics
Stromal Cells / drug effects*,  metabolism
Transcription, Genetic / drug effects,  genetics
Tretinoin / pharmacology*
Up-Regulation / drug effects
Grant Support
Reg. No./Substance:
0/Connexin 43; 0/RNA, Messenger; 302-79-4/Tretinoin; 50-76-0/Dactinomycin; 66-81-9/Cycloheximide; EC Phosphatase 2

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