Validation of the epigenetic reader bromodomain-containing protein 4 (BRD4) as a therapeutic target for treatment of airway remodeling

Abstract

Structural remodeling is central to the initiation and progression of many chronic lung diseases, representing an important unmet need. We examine the evidence supporting bromodomain-containing protein 4 (BRD4) as a validated biological target for treatment of airway remodeling. In epithelial cells and fibroblasts, BRD4 serves as a scaffold for chromatin remodeling complexes in active super-enhancers. In response to inflammatory stimuli, BRD4 is repositioned to innate and mesenchymal genes activating their production. Proof-of-concept studies show promising benefit of selective BRD4 inhibitors in disrupting epithelial mesenchymal transition and myofibroblast transition in diverse models of lung injury. Recent identification of biomarkers of BRD4 provides a basis for further drug development for application in viral-induced airway inflammation, COPD and interstitial lung diseases.