Credit: Association of Basic Medical Sciences of FBIH

Asthma is a chronic respiratory condition marked by airway inflammation, narrowing, and episodes of wheezing, coughing, and shortness of breath. It affects millions of people worldwide and continues to rise in prevalence, posing a growing challenge for health care systems.

While inhaled corticosteroids, bronchodilators, and newer biologic therapies help control symptoms, many patients—particularly those with severe forms—do not achieve full relief. This underscores the need for deeper insights into the biological mechanisms behind the disease.

A new study has uncovered how a specific molecular pathway may fuel inflammation and tissue damage in asthma. Researchers report that a protein called EPAS1, activated through the JAK2/STAT3 signaling pathway, drives a form of cell death known as ferroptosis in airway cells.

The study has been published in Biomolecules and Biomedicine.

Ferroptosis, caused by iron-dependent oxidative stress, has recently been linked to several chronic lung conditions but has not been fully understood in the context of asthma.

By combining bioinformatics analysis with laboratory experiments, the team identified five key genes linked to ferroptosis in asthma, with EPAS1 emerging as a critical player.

They showed that activation of the JAK2/STAT3 pathway increased EPAS1 levels, which in turn promoted oxidative stress, airway inflammation, and structural changes in the lungs. Blocking components of this pathway reduced these damaging effects, pointing to a potential new therapeutic target.

Importantly, the study highlights both opportunities and challenges. Current asthma treatments focus on broad immune suppression, which can leave residual symptoms and side effects.

By contrast, targeting ferroptosis and its regulators could provide a more precise approach. However, these findings remain at an early stage, and further research is needed to validate their clinical relevance and determine whether inhibitors of ferroptosis or EPAS1 could be developed into safe and effective treatments.

The discovery adds to growing evidence that cell death pathways are deeply involved in asthma pathogenesis. Understanding how ferroptosis interacts with immune responses not only offers the potential for better treatments, but also expands knowledge of the complex mechanisms driving this common yet diverse disease.

More information: Lili Liu et al, EPAS1 amplifies asthma pathogenesis through JAK2/STAT3-mediated ferroptosis and inflammation, Biomolecules and Biomedicine (2025). DOI: 10.17305/bb.2025.11334