An orally bioavailable BRD4 inhibitor disrupts expansion of a pathogenic epithelial-mesenchymal niche in bleomycin-induced fibrosis.

ABSTRACT:

Background

Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive and fatal disease with few effective therapies available. Fibrosis is driven, in part, by cell-state transitions of epithelial progenitors within the airways that repopulate the injured alveoli. This alveolar atypia affects gas exchange and stimulates ECM production. We sought to examine the role of BRD4 signaling in progenitor expansion in bleomycin-induced lung injury.

Methods

Activation of the Bromodomain-containing protein 4 (BRD4) epigenetic regulator in distinct stem cell populations was quantitated in a high-resolution scRNA-seq time course of bleomycin-induced injury, and confirmed in scRNA-seq studies in human IPF. A potent, selective, and orally bioavailable BRD4 inhibitor (BRD4i, ZL0969)

SUBMITTER: Skibba M 

PROVIDER: S-EPMC12225180 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature