Inhibiting epithelial cell extrusion and inflammation synergistically reverses asthmatic airway remodelling
Bagley, D. C.; Russell, T.; Martinez-Nunez, R. T.; Marcotti, S.; Rosenblatt, J.
Show 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.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Inhibition of acute lung inflammation by a neuroimmune circuit induced by vagal nerve stimulation. 95%
- Prolonged airway explant culture enables study of health, disease, and viral pathogenesis 94%
- Single Cell RNA-seq reveals ectopic and aberrant lung resident cell populations in Idiopathic Pulmonary Fibrosis 93%
Similar papers in this journal
Similar papers in this journal
- MUC5AC drives COPD exacerbation severity through amplification of virus-induced airway inflammation 94%
- Myeloid-mesenchymal crosstalk drives Arg1-dependent profibrotic metabolism via ornithine in lung fibrosis 93%
- A20's Linear Ubiquitin Binding Motif Restrains Pathogenic Activation of TH17/22 cells and IL-22 Driven Enteritis 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.