# Investigation of the mechanistic impact of CBL0137 on airway remodeling in asthma

## TL;DR

This study explores how CBL0137 affects airway remodeling in asthma, showing it reduces airway thickening and cell proliferation in mice.

## Contribution

The novel contribution is demonstrating CBL0137's anti-remodeling effects on airway smooth muscle cells in asthma for the first time.

## Key findings

- CBL0137 reduced airway resistance and collagen deposition in asthmatic mice.
- It inhibited airway smooth muscle cell proliferation and induced apoptosis in vitro.
- CBL0137 modulated key proteins like cyclin-B1 and caspase-3 in asthma models.

## Abstract

Bronchial asthma, a chronic inflammatory airway disease, is characterized by airway remodeling, including thickening of the airway smooth muscle layer, primarily due to abnormal proliferation of airway smooth muscle cells (ASMCs). CBL0137 (Curaxin-137 hydrochloride), a histone chaperone facilitate chromatin transcription (FACT) inhibitor, has demonstrated anti-tumor properties, including inhibition of proliferation, promotion of apoptosis, and increased autophagy. However, its effects on ASMCs and airway remodeling remain unexplored.

Asthma models were established using ovalbumin (OVA) in female C57BL/6 J mice, with therapeutic interventions using CBL0137 and budesonide. Lung tissues were analyzed using Hematoxylin and eosin (H&E), PAS, Masson’s trichrome, and α-SMA immunofluorescence staining. ASMCs extracted from Sprague–Dawley rats were cultured in vitro experiments, with phenotypic changes assessed via flow cytometry. Gene and protein expressions were analyzed using RT-PCR and Western blotting.

CBL0137 significantly reduced airway resistance, goblet cell proliferation, alveolar collagen deposition, and airway smooth muscle layer thickening in asthmatic mice. In vitro, CBL0137 inhibited ASMC proliferation and induced apoptosis, downregulating cyclin-B1, Cdc2, and Bcl-2 while upregulating caspase-3.

CBL0137 mitigates airway remodeling of asthmatic mice by modulating ASMC proliferation and apoptosis, presenting a potential therapeutic strategy for asthma treatment.

The online version contains supplementary material available at 10.1186/s12890-025-03596-y.