Document Detail

HIF1α and pancreatic β-cell development.
MedLine Citation:
PMID:  22426121     Owner:  NLM     Status:  MEDLINE    
During early embryogenesis, the pancreas shows a paucity of blood flow, and oxygen tension, the partial pressure of oxygen (pO(2)), is low. Later, the blood flow increases as β-cell differentiation occurs. We have previously reported that pO(2) controls β-cell development in rats. Here, we checked that hypoxia inducible factor 1α (HIF1α) is essential for this control. First, we demonstrated that the effect of pO(2) on β-cell differentiation in vitro was independent of epitheliomesenchymal interactions and that neither oxidative nor energetic stress occurred. Second, the effect of pO(2) on pancreas development was shown to be conserved among species, since increasing pO(2) to 21 vs. 3% also induced β-cell differentiation in mouse (7-fold, P<0.001) and human fetal pancreas. Third, the effect of hypoxia was mediated by HIF1α, since the addition of an HIF1α inhibitor at 3% O(2) increased the number of NGN3-expressing progenitors as compared to nontreated controls (9.2-fold, P<0.001). In contrast, when we stabilized HIF1α by deleting ex vivo the gene encoding pVHL in E13.5 pancreas from Vhl floxed mice, Ngn3 expression and β-cell development decreased in such Vhl-deleted pancreas compared to controls (2.5 fold, P<0.05, and 6.6-fold, P<0.001, respectively). Taken together, these data demonstrate that HIF1α exerts a negative control over β-cell differentiation.
Mylène Heinis; Andrea Soggia; Camille Bechetoille; Marie-Thérèse Simon; Carole Peyssonnaux; Pierre Rustin; Raphael Scharfmann; Bertrand Duvillié
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-16
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  26     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-29     Completed Date:  2012-09-20     Revised Date:  2014-06-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2734-42     Citation Subset:  IM    
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MeSH Terms
Anoxia / embryology,  pathology,  physiopathology
Base Sequence
Basic Helix-Loop-Helix Transcription Factors / genetics
Cell Differentiation / genetics,  physiology
DNA Primers / genetics
Embryonic Development / genetics,  physiology
Energy Metabolism
Gene Expression Regulation, Developmental
Hypoxia-Inducible Factor 1, alpha Subunit / deficiency,  genetics,  physiology*
Insulin-Secreting Cells / cytology*,  physiology*
Islets of Langerhans / cytology,  embryology,  physiology
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Nerve Tissue Proteins / genetics
Oxidative Stress
Rats, Wistar
Signal Transduction
Species Specificity
Von Hippel-Lindau Tumor Suppressor Protein / genetics,  physiology
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/DNA Primers; 0/HIF1A protein, human; 0/Hif1a protein, mouse; 0/Hif1a protein, rat; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Nerve Tissue Proteins; 0/Neurog3 protein, mouse; EC protein, mouse; EC Hippel-Lindau Tumor Suppressor Protein

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