Authors
Bagley, D. C., Russell, T., Martinez-Nunez, R. T., Marcotti, S., Rosenblatt, J.
Abstract
Asthma is a prevalent inflammatory disease marked by life-threatening airway constriction. Current therapies alleviate symptoms by relaxing airway smooth muscle and reducing inflammation but fail to address the underlying airway remodelling, which drives hyper-responsiveness and lung function decline. We previously showed that bronchoconstriction mechanics trigger pathological cell extrusion, wounding the epithelial barrier and perpetuating inflammation. Here, we reveal that a vicious cycle of epithelial damage and inflammation, perpetuates airways in a chronically wounded state. By inhibiting both extrusion and inflammation in mice with established airway asthma symptoms, we synergistically reverse airway remodelling and hyperresponsiveness to methacholine challenge. Moreover, this dual treatment reverts asthmatic transcriptomic and proteomic profiles to healthy states, restoring normal airway function. Our findings offer a novel therapeutic approach to not only halt but reverse asthma progression.
Preprint server:
bioRxiv
The authors list and abstract were imported from bioRxiv on 12 Nov 2025.
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