title: Repression of the Central Splicing Regulator RBFox2 Is Functionally Linked to Pressure Overload-Induced Heart Failure.
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.
authors.affiliation: Department of Cellular and Molecular Medicine University of California, San Diego, La Jolla, CA 92093-0651, USA.
authors.forename: Chaoliang
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of Cellular and Molecular Medicine University of California, San Diego, La Jolla, CA 92093-0651, USA.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Qiu
authors.affiliation: Department of Cellular and Molecular Medicine University of California, San Diego, La Jolla, CA 92093-0651, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cellular and Molecular Medicine University of California, San Diego, La Jolla, CA 92093-0651, USA.
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Cellular and Molecular Medicine University of California, San Diego, La Jolla, CA 92093-0651, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Medicine University of California, San Diego, La Jolla, CA 92093-0651, USA.
authors.forename: Kunfu
authors.initials: K
authors.lastname: Ouyang
authors.affiliation: Department of Medicine University of California, San Diego, La Jolla, CA 92093-0651, USA.
authors.forename: Indroneal
authors.initials: I
authors.lastname: Banerjee
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Caimei
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Biyi
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Cellular and Molecular Medicine University of California, San Diego, La Jolla, CA 92093-0651, USA.
authors.forename: Hairi
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Medicine University of California, San Diego, La Jolla, CA 92093-0651, USA.
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.
authors.forename: Long-Sheng
authors.initials: LS
authors.lastname: Song
authors.affiliation: Department of Cellular and Molecular Medicine University of California, San Diego, La Jolla, CA 92093-0651, USA; Institute of Genomic Medicine, University of California, San Diego, La Jolla, CA 92093-0651, USA. Electronic address: xdfu@ucsd.edu.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Fu