Journal article
Repression of the Central Splicing Regulator RBFox2 Is Functionally Linked to Pressure Overload-Induced Heart Failure
Cell reports (Cambridge), Vol.10(9), pp.1521-1533
03/10/2015
DOI: 10.1016/j.celrep.2015.02.013
PMCID: PMC4559494
PMID: 25753418
Abstract
Heart failure is characterized by the transition from an initial compensatory response to decompensation, which can be partially mimicked by transverse aortic constriction (TAC) in rodent models. Numerous signaling molecules have been shown to be part of the compensatory program, but relatively little is known about the transition to decompensation that leads to heart failure. Here, we show that TAC potently decreases the RBFox2 protein in the mouse heart, and cardiac ablation of this critical splicing regulator generates many phenotypes resembling those associated with decompensation in the failing heart. Global analysis reveals that RBFox2 regulates splicing of many genes implicated in heart function and disease. A subset of these genes undergoes developmental regulation during postnatal heart remodeling, which is reversed in TAC-treated and RBFox2 knockout mice. These findings suggest that RBFox2 may be a critical stress sensor during pressure overload-induced heart failure.
Details
- Title: Subtitle
- Repression of the Central Splicing Regulator RBFox2 Is Functionally Linked to Pressure Overload-Induced Heart Failure
- Creators
- Chaoliang Wei - University of California, San DiegoJinsong Qiu - University of California, San DiegoYu Zhou - University of California, San DiegoYuanchao Xue - University of California, San DiegoJing Hu - University of California, San DiegoKunfu Ouyang - University of California, San DiegoIndroneal Banerjee - University of California, San DiegoCaimei Zhang - Roy J. and Lucille A. Carver College of MedicineBiyi Chen - Roy J. and Lucille A. Carver College of MedicineHairi Li - University of California, San DiegoJu Chen - University of California, San DiegoLong-Sheng Song - Roy J. and Lucille A. Carver College of MedicineXiang-Dong Fu - University of California, San Diego
- Resource Type
- Journal article
- Publication Details
- Cell reports (Cambridge), Vol.10(9), pp.1521-1533
- Publisher
- Elsevier
- DOI
- 10.1016/j.celrep.2015.02.013
- PMID
- 25753418
- PMCID
- PMC4559494
- ISSN
- 2211-1247
- eISSN
- 2211-1247
- Number of pages
- 13
- Grant note
- R01HG004659 / NATIONAL HUMAN GENOME RESEARCH INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Human Genome Research Institute (NHGRI) R01HL090905 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) R01GM049369 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) GM049369; HG004659; HG007005 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 03/10/2015
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984293086902771
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