Pharmacoproteomics reveal novel protective activity of bromodomain containing 4 inhibitors on vascular homeostasis in TLR3-mediated airway remodeling.

ABSTRACT: Small molecule inhibitors of the epigenetic regulator bromodomain-containing protein 4 (BRD4) are potential therapeutics for viral and allergen-induced airway remodeling. A limitation of their preclinical advancement is the lack of detailed understanding of mechanisms of action and biomarkers of effect. We report a systems-level pharmacoproteomics in a standardized murine model of toll-like receptor TLR3-NFκB/RelA innate inflammation in the absence or presence of a highly selective BRD4 inhibitor (ZL0454) or nonselective bromodomain and extraterminal domain inhibitor (JQ1). Proteomics of bronchoalveolar lavage fluid (BALF) secretome and exosomal proteins from this murine model revealed increased, selective, capillary leak associated with pericyte-myofibroblast transition, a phenomenon bloc

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC6699176 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature