Transforming growth factor β-activated kinase 1 signaling pathway critically regulates myocardial survival and remodeling.

ABSTRACT:

Background

Programmed necrosis (necroptosis) plays an important role in development, tissue homeostasis, and disease pathogenesis. The molecular mechanisms that regulate necroptosis in the heart and its physiological relevance in myocardial remodeling and heart failure remain largely unknown.

Methods and results

Here, we identified an obligate function for TAK1 (transforming growth factor β-activated kinase 1, gene name Map3k7) in regulating necroptotic myocyte death, myocardial remodeling, and heart failure propensity. Cardiac-specific ablation of Map3k7 in mice induced spontaneous apoptosis and necroptosis that led to adverse remodeling and heart failure, and these effects were abolished by ablation of tumor necrosis factor receptor-1. Mechanistically, TAK1 functions as a

SUBMITTER: Li L 

PROVIDER: S-EPMC4302054 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature