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.

中文翻译：

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验证表观遗传阅读器含溴结构域的蛋白质4（BRD4）作为治疗气道重塑的治疗靶标。

结构重塑对于许多慢性肺部疾病的发生和发展至关重要，这代表了重要的未满足需求。我们检查了支持含溴结构域蛋白4（BRD4）作为治疗气道重塑的经过验证的生物学靶标的证据。在上皮细胞和成纤维细胞中，BRD4作为活性超级增强子中染色质重塑复合物的支架。响应炎症刺激，将BRD4重新定位为先天和间充质基因，从而激活其产生。概念验证研究表明，在不同的肺损伤模型中，选择性BRD4抑制剂在破坏上皮间质转化和成纤维细胞转化方面具有令人鼓舞的益处。BRD4生物标志物的最新鉴定为进一步开发用于病毒性气道炎症的药物奠定了基础，