Scientists Discover JAK2/STAT3/EPAS1 Pathway as a Key Driver in Severe Asthma

Recent research has shed light on the complex biological mechanisms underlying severe asthma, a chronic respiratory disease characterized by airway inflammation, narrowing, and recurrent episodes of wheezing, coughing, and shortness of breath. The study highlights the pivotal role of the JAK2/STAT3/EPAS1 signaling axis in exacerbating the condition.

Asthma affects millions globally, and despite advancements in treatment with inhaled steroids, bronchodilators, and biologics, certain severe cases remain resistant to therapy, emphasizing the need for new therapeutic targets. The latest findings reveal that the protein EPAS1, also known as HIF-2α, becomes activated through the JAK2/STAT3 pathway, leading to increased inflammation and tissue damage in the lungs.

A key discovery of this research is the role of ferroptosis, a form of iron-dependent cell death driven by oxidative stress, which contributes to airway damage in asthma. The researchers combined bioinformatics with laboratory experiments to identify five genes linked to ferroptosis, with EPAS1 emerging as a crucial regulator.

Activation of the JAK2/STAT3 pathway was shown to elevate EPAS1 levels, promoting oxidative stress and lung inflammation. When components of this pathway were blocked, the damaging effects were significantly reduced, pointing to potential new intervention strategies.

This research opens the possibility of developing targeted therapies that inhibit ferroptosis or block the JAK2/STAT3/EPAS1 axis, offering more precise treatment options for severe asthma. However, further studies are necessary to validate these targets and ensure the safety and efficacy of future drugs.

Understanding the involvement of cell death pathways like ferroptosis in asthma advances our knowledge of the disease's underlying biology. Such insights could lead to more personalized approaches, improving outcomes for patients with stubborn, treatment-resistant asthma.

More details can be found in the study published in Biomolecules and Biomedicine.

Source: https://medicalxpress.com/news/2025-09-reveal-jak2stat3epas1-axis-driver-severe.html