A computational model of cardiac fibroblast signaling predicts context-dependent drivers of myofibroblast differentiation.

ABSTRACT: Cardiac fibroblasts support heart function, and aberrant fibroblast signaling can lead to fibrosis and cardiac dysfunction. Yet how signaling molecules drive myofibroblast differentiation and fibrosis in the complex signaling environment of cardiac injury remains unclear. We developed a large-scale computational model of cardiac fibroblast signaling in order to identify regulators of fibrosis under diverse signaling contexts. The model network integrates 10 signaling pathways, including 91 nodes and 134 reactions, and it correctly predicted 80% of independent previous experiments. The model predicted key fibrotic signaling regulators (e.g. reactive oxygen species, tissue growth factor β (TGFβ) receptor), whose function varied depending on the extracellular environment. We characterized how

SUBMITTER: Zeigler AC 

PROVIDER: S-EPMC4861657 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature