Document Detail

Vitamin D and vitamin A receptor expression and the proliferative effects of ligand activation of these receptors on the development of pancreatic progenitor cells derived from human fetal pancreas.
MedLine Citation:
PMID:  20354914     Owner:  NLM     Status:  MEDLINE    
The growth and development of pancreatic islet cells are regulated by various morphogens. Vitamin A modulates in vitro differentiation of islet cells and vitamin D affects beta-cell insulin secretion, while both vitamin ligands act through heterodimerization with the retinoid X receptor (RXR). However, their effects in modulating pancreatic development have not been determined. In this study, cultured human pancreatic progenitor cells (PPCs) isolated from human fetal pancreas were stimulated to differentiate into islet-like cell clusters (ICCs). RT-PCR, Western blotting and immunocytochemistry were used to examine the expression and localization of vitamin D receptor (VDR), retinoic acid receptor (RAR), and RXR in PPCs. The effects of added all-trans retinoic acid (atRA, a form of vitamin A), calcitriol (activated vitamin D) and of these ligands together on PPC cell viability, proliferation and apoptosis were assessed by MTT, BrdU and ELISA assays, respectively. Post-treatment neurogenin-3 (NGN3) expression, necessary for islet-cell lineage development, was examined by real-time RT-PCR. Results showed that RAR, RXR and VDR were expressed in PPCs. RAR and RXR were localized in nuclei, and the VDR in nuclei, cytoplasm and plasma membrane. atRA and calcitriol each increased PPC viability and proliferation; atRA additionally decreased PPC apoptosis. Co-addition of atRA and calcitriol had no additive effects on cell viability but did increase ngn3 responses. In conclusion, RAR, RXR and VDR are expressed in human fetal PPCs and PPC proliferation can be promoted by calcitriol, atRA or both together, data valuable for elucidating mechanisms underlying islet development and for developing clinical islet transplantation.
Ka Yan Ng; Man Ting Ma; Kwan Keung Leung; Po Sing Leung
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Stem cell reviews     Volume:  7     ISSN:  1558-6804     ISO Abbreviation:  Stem Cell Rev     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-01-24     Completed Date:  2011-04-28     Revised Date:  2014-01-13    
Medline Journal Info:
Nlm Unique ID:  101255952     Medline TA:  Stem Cell Rev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  53-63     Citation Subset:  IM    
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MeSH Terms
Apoptosis / drug effects
Basic Helix-Loop-Helix Transcription Factors / genetics,  metabolism
Calcitriol / pharmacology
Cell Proliferation / drug effects
Cell Survival / drug effects
Cytochrome P-450 Enzyme System / metabolism
Fetus / cytology*
Nerve Tissue Proteins / genetics,  metabolism
Pancreas / cytology*,  embryology*
RNA, Messenger / genetics,  metabolism
Receptors, Calcitriol / genetics,  metabolism*
Receptors, Retinoic Acid / genetics,  metabolism*
Retinoid X Receptors / genetics,  metabolism*
Stem Cells / cytology,  drug effects,  metabolism*
Steroid Hydroxylases / metabolism
Tretinoin / pharmacology
Up-Regulation / drug effects
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Ligands; 0/NEUROG3 protein, human; 0/Nerve Tissue Proteins; 0/RNA, Messenger; 0/Receptors, Calcitriol; 0/Receptors, Retinoic Acid; 0/Retinoid X Receptors; 5688UTC01R/Tretinoin; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.-/Steroid Hydroxylases; EC D 24-hydroxylase; EC acid 4-hydroxylase; FXC9231JVH/Calcitriol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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