Idiopathic Subglottic Stenosis Is Associated With More Frequent and Abnormal Squamous Metaplasia

Area of Science:

• Pulmonary Medicine
• Cell Biology
• Genomics

Background:

• Idiopathic subglottic stenosis (iSGS) is a rare but serious condition affecting the airway.
• The underlying pathophysiology of iSGS remains incompletely understood, particularly the role of epithelial cell changes.

Purpose of the Study:

• To investigate the molecular differences in subglottic mucosal tissue between iSGS patients and controls.
• To identify specific genes and pathways involved in the pathogenesis of iSGS.
• To explore potential therapeutic strategies targeting epithelial cell differentiation.

Main Methods:

• RNA sequencing of subglottic and tracheal mucosal samples from iSGS patients and controls.
• Validation of gene expression differences at the protein level using immunohistochemistry.
• In vitro functional assays with primary subglottic epithelial cells from iSGS patients and healthy donors.

Main Results:

• Seven genes were found to be upregulated in the subglottic region of iSGS patients.
• Epithelial cell differentiation and cornification pathways, involving IVL, SPRRB1B, and KRT16, were significantly enriched.
• Histological and immunohistochemical analyses revealed squamous metaplasia and increased proliferation in iSGS epithelial cells, indicating basal cell dysfunction.

Conclusions:

• Abnormal squamous differentiation of epithelial cells is a key factor in iSGS pathogenesis.
• The identification of specific molecular pathways and cell dysfunction provides a basis for developing targeted therapies for iSGS.