Publication Date:
2012-11-20
Description:
The epicardium encapsulates the heart and functions as a source of multipotent progenitor cells and paracrine factors essential for cardiac development and repair. Injury of the adult heart results in reactivation of a developmental gene program in the epicardium, but the transcriptional basis of epicardial gene expression has not been delineated. We established a mouse embryonic heart organ culture and gene expression system that facilitated the identification of epicardial enhancers activated during heart development and injury. Epicardial activation of these enhancers depends on a combinatorial transcriptional code centered on CCAAT/enhancer binding protein (C/EBP) transcription factors. Disruption of C/EBP signaling in the adult epicardium reduced injury-induced neutrophil infiltration and improved cardiac function. These findings reveal a transcriptional basis for epicardial activation and heart injury, providing a platform for enhancing cardiac regeneration.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613149/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3613149/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Huang, Guo N -- Thatcher, Jeffrey E -- McAnally, John -- Kong, Yongli -- Qi, Xiaoxia -- Tan, Wei -- DiMaio, J Michael -- Amatruda, James F -- Gerard, Robert D -- Hill, Joseph A -- Bassel-Duby, Rhonda -- Olson, Eric N -- 1K99HL114738/HL/NHLBI NIH HHS/ -- HL100401-01/HL/NHLBI NIH HHS/ -- K99 HL114738/HL/NHLBI NIH HHS/ -- R01 HL077439/HL/NHLBI NIH HHS/ -- R01 HL093039/HL/NHLBI NIH HHS/ -- R01 HL111665/HL/NHLBI NIH HHS/ -- U01 HL100401/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2012 Dec 21;338(6114):1599-603. doi: 10.1126/science.1229765. Epub 2012 Nov 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23160954" target="_blank"〉PubMed〈/a〉
Keywords:
Aldehyde Oxidoreductases/genetics/metabolism
;
Animals
;
Binding Sites
;
CCAAT-Enhancer-Binding Protein-beta/genetics/metabolism
;
CCAAT-Enhancer-Binding Protein-delta/genetics/metabolism
;
CCAAT-Enhancer-Binding Proteins/genetics/*metabolism
;
Enhancer Elements, Genetic
;
Female
;
*Gene Expression Regulation
;
Gene Expression Regulation, Developmental
;
Heart/embryology/*physiopathology
;
Male
;
Mice
;
Mice, Transgenic
;
Models, Genetic
;
Myocardial Contraction
;
Myocardial Infarction/*genetics/metabolism
;
Myocardial Reperfusion Injury/*genetics/metabolism
;
Neutrophil Infiltration
;
Oligonucleotide Array Sequence Analysis
;
Organ Culture Techniques
;
Pericardium/cytology/*embryology/*metabolism
;
Signal Transduction
;
Uroplakin III/genetics/metabolism
;
Ventricular Remodeling
;
WT1 Proteins/genetics/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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