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E2F1-regulated miR-30b suppresses Cyclophilin D and protects heart from ischemia/reperfusion injury and necrotic cell death.
MedLine Citation:
PMID:  25301066     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cardiovascular disease remains the leading cause of morbidity and mortality worldwide. Cell death is a hallmark characteristic of various cardiac diseases, including myocardial infarction and heart failure. Emerging evidences suggest that necrosis is programmed and is one of the main forms of cell death in the pathological process in cardiac diseases. However, the molecular components regulating programmed necrosis in heart remain largely unidentified. Here we report that miR-30b, Cyclophilin D (CypD) and E2F1 constitute an axis that regulates necrosis. The results show that knockdown of CypD attenuated necrosis in the cellular model and also myocardial infarction in the animal model. miR-30b suppresses the translation of CypD and thus inhibits CypD-mediated necrotic cell death in cardiomyocytes. Cardiac-specific miR-30b transgenic mice exhibit reduced necrosis and myocardial infarct size upon ischemia/reperfusion (I/R) injury. Further, we identify that E2F1 transcriptionally represses miR-30b expression. Knockdown of E2F1 in cardiomyocytes inhibits necrotic cell death, and E2F1 knockout mice show reduced necrosis and myocardial infarct size upon I/R. Our present study identifies a novel signaling pathway composed of E2F1, miR-30b and CypD that regulates myocardial necrosis. This discovery will not only provide de novo regulators in the necrotic process but will also shed new light on the effective therapy of myocardial infarction and heart failure.Cell Death and Differentiation advance online publication, 10 October 2014; doi:10.1038/cdd.2014.165.
Authors:
K Wang; T An; L-Y Zhou; C-Y Liu; X-J Zhang; C Feng; P-F Li
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-10
Journal Detail:
Title:  Cell death and differentiation     Volume:  -     ISSN:  1476-5403     ISO Abbreviation:  Cell Death Differ.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-10-10     Completed Date:  -     Revised Date:  2014-10-11    
Medline Journal Info:
Nlm Unique ID:  9437445     Medline TA:  Cell Death Differ     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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