The airway epithelia of people with idiopathic pulmonary fibrosis (IPF) are biophysically distinct from that of healthy people, based on a study published in Nature Communications.
“Our data illustrate the active mechanisms regulating airway epithelial-driven fibrosis and identify targets to modulate disease progression,” stated Ian T. Stancil and the co-authors of the study.
The pathogenic role of the airway epithelium in IPF is not known. Here, the researchers investigated the primary differences in the epithelial cells of the airways in patients with IPF and healthy people.
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Using the air-liquid-interface (ALI) culture system, they found that the IPF epithelia had a significantly delayed jamming transition compared to healthy epithelia.
The jamming transition is a tissue-wide biophysical phenomenon where a fluid-like or unjammed phase transitions into a solid-like or jammed phase. The jamming transition is implicated in biological processes, such as body-axis elongation during development in vertebrates, as well as in pathological mechanisms, such as cancer metastasis and asthma pathogenesis. In the unjammed phase, groups of cells can collectively migrate and cross large distances.
“This prolonged unjammed phase in IPF could be indicative of a persistent disruption in epithelial homeostasis,” the researchers reported.
The team also investigated the genetic factors and signaling pathways that may be involved in delayed jamming. They found that the expression of ERBB family receptors and YES-associated protein (YAP) target genes were higher in the unjammed phase. They concluded that the “extended unjammed phase was associated with a failure to properly moderate ERBB-YAP signaling.”
The ERBB-YAP axis is a “specific and modifiable driver of prolongation of the unjammed-to-jammed transition in IPF epithelia,” the researchers said, emphasizing that modifying the ERBB-YAP axis could reverse the biophysical defects of IPF epithelia and constitute a potential new therapeutic target to delay the progression of the disease.
Stancil IT, Michalski JE, Davis-Hall D, et al. Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional. Nat Commun. 2021;27;12(1):4566. doi:10.1038/s41467-021-24853-8