当前位置： SCI文献检索 > CARDIOVASCULAR RESEARCH期刊下所有文献 > GATA4 expression is primarily regulated via a miR-26b-dependent post-transcriptional mechanism during cardiac hypertrophy.

GATA4 expression is primarily regulated via a miR-26b-dependent post-transcriptional mechanism during cardiac hypertrophy.

Abstract：

AIMS:GATA4 is a transcription factor that is up-regulated during cardiac hypertrophy and plays a fundamental role in myocyte growth and survival. In this study, we investigate the transcriptional vs. post-transcriptional mechanisms that are involved in regulating GATA4 in the heart during neonatal and pressure overload-induced hypertrophic growth. METHODS AND RESULTS:GATA4 protein is significantly higher during pressure overload-induced (2.9 ± 0.4-fold) and neonatal (6.8 ± 1-fold) hypertrophic growth vs. the normal adult mouse heart. Using RNA polymerase II immunoprecipitation combined with deep sequencing, we confirmed that active transcription of the Gata4 gene remained unchanged during hypertrophy, whereas it was two-fold higher in the neonatal vs. adult heart, commensurate with the mRNA levels. These results suggested a post-transcriptional mode of regulation of its expression, which prompted the identification of a conserved sequence in its 3'-untranslated region that was responsible for reduced translation via miR-26b. Overexpression of miR-26b reduced GATA4-dependent transcription, endothelin-induced hypertrophy, and sensitized the cells to apoptotic insults. Additionally, miR-26b targeted phospholipase C-β1, which, in turn, inhibited miR-26b expression, creating a double-negative feedback loop. Accordingly, overexpression of miR-26b in the heart inhibited up-regulation of its targets and the development of hypertrophy. However, knockdown of miR-26b is not sufficient for inducing hypertrophy. CONCLUSION:Down-regulation of miR-26b in the heart is required for the up-regulation of GATA4 and the induction of pressure-induced cardiac hypertrophy. The results also underscore the functional relevance of miRNAs in regulating gene expression during cardiac hypertrophy.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Han M,Yang Z,Sayed D,He M,Gao S,Lin L,Yoon S,Abdellatif M

doi

10.1093/cvr/cvs001

subject

Has Abstract

pub_date

2012-03-15 00:00:00

pages

645-54

issue

eissn

0008-6363

issn

1755-3245

pii

cvs001

journal_volume

pub_type

杂志文章

在线工具

GATA4 expression is primarily regulated via a miR-26b-dependent post-transcriptional mechanism during cardiac hypertrophy.