Asthma is About More Than Just Inflammation

Treatments for asthma primarily focus on reducing inflammation, but researchers at the Harvard T.H. Chan School of Public Health suggest there may be more to the story. They believe it’s time to turn the spotlight on bronchoconstriction as well.

In a study published in Nature Communications, researchers found that a protein termed Hic-5 converts the muscle contraction and increased cellular pressure observed in bronchoconstriction into biochemical signals that drive a self-perpetuating cycle of worsening bronchoconstriction, which may be as problematic as inflammation.

Hic-5 was identified in an experimental study in which investigators placed airway epithelial cells from human donors into culture and then applied mechanical forces simulating bronchoconstriction. Further study revealed that the protein promotes the formation of stress fibers, which increase intracellular tension and activate biochemical signaling within cells.

When Hic-5 was silenced, the biochemical signaling was eased.

A computational model was used to analyze gene and pathway data to identify key molecules involved in the bronchoconstriction loop, revealing that Hic-5 plays a significant role in this process. Publicly available human datasets from asthma patients experiencing bronchoconstriction were used to validate the findings.

The authors believe the study may help explain why up to 25% of asthma patients don’t respond well to standard treatments targeting inflammation. Bronchoconstriction may be the problem, and new strategies to interrupt the mechanical-to-chemical signaling pathway that perpetuates bronchoconstriction could significantly improve asthma care and outcomes.

“Together, our findings provide critical mechanistic insights into how mechanical stress shapes epithelial responses and highlight Hic-5 as a potential therapeutic target for mitigating disease progression in asthma,” wrote the authors. “Moreover, our data advance our understanding of how dysregulated mechanical forces drive disease progression, offering mechanistic insights into chronic conditions governed by mechanotransduction beyond the lung.” 

Highlighted in RC Buzz February 9, 2026