THE ROLE OF TCF21 IN CARDIAC FIBROBLAST CELL NUMBER AND EXTRACELLULAR MATRIX REMODELING

Abstract

Heart disease remains a major health burden in the United States, and complications from injury to the heart, including fibrosis, may lead to heart failure. Cardiac fibroblasts are the cells most intimately implicated in the cardiac injury response. Elucidating the molecular basis behind cardiac fibroblast injury phenotypes can help us to develop more targeted approaches for treating adverse myocardial remodeling. Cardiac fibroblasts reside within the heart and, during homeostatic conditions, will deposit extracellular matrix (ECM) and maintain vascularity. However, when activated following external stimuli, fibroblasts proliferate, remodel ECM, and recruit inflammatory cells to the area. Excessive deposition of ECM proteins can accelerate the progression of uncontrolled fibrosis to heart failure. Our lab has identified transcription factor 21 (Tcf21) as a critical gene required for epicardial cardiac fibroblast differentiation. Based on preliminary data and previously published work, Tcf21 has been shown to regulate proliferation and ECM remodeling. My hypothesis is that cardiac fibroblast specific deletion of Tcf21 will reduce cardiac fibroblast numbers and ECM remodeling, which is exacerbated following injury. In my dissertation work, I have discovered the role of Tcf21 in adult mouse hearts with a transgenic mouse model after cardiac injury.