A near-infrared fluorescent probe was used to evaluate the role of histone deacetylase in pulmonary fibrosis cells and mice

Abstract

Idiopathic pulmonary fibrosis (IPF) is a common and serious pulmonary fibrosis disease, the pathogenesis of IPF is closely related to a variety of biological small molecules and proteins, Histone deacetylases (HDACs) play an important role in inhibiting apoptosis and promoting pulmonary fibrosis. Here, we propose Cy-HDAC, (a HDACs fluorescent probe), which is selective and sensitive to HDACs and can be used to detect real-time fluctuations in HDACs activity in cells and mouse models. Our results suggest that HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) treatment in the model group of pulmonary fibrosis leads to enhanced acetylation of histone H3, which allows increased transcription of some apoptosis-related proteins, promoting the activation of apoptotic protein Bak and mitochondria intrinsic apoptotic pathways, while the reduction of anti-apoptotic protein Bcl-xL promotes fibroblast apoptosis. In the bleomycin-induced pulmonary fibrosis mouse model, we found that pulmonary fibrosis severity was reduced in the SAHA-treated group, and SAHA combined with pirfenidone was superior to pirfenidone alone. Therefore, HDACs levels in IPF may provide a new detection possibility for IPF diagnosis, and HDACs may provide a novel alternative for the treatment of IPF.