The interplay of airway epithelium and biomechanical stress in pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive and often fatal lung disease characterized by the scarring and stiffening of lung tissue. While its exact cause remains elusive, emerging evidence underscores the significant role of mechanical forces and aberrant epithelial responses in its pathogenesis. The airway epithelium serves as a critical barrier and regulator of lung function, exhibiting abnormal responses to mechanical stress. Recent studies suggest that the abnormal airway epithelial response to mechanical stressors contributes to the progression of IPF and serves as an early indicator of disease onset. Understanding the complex interplay between mechanical forces and these cells in IPF not only sheds light on disease mechanisms but also opens avenues for novel therapeutic interventions targeting these pathways. The goal of this review is to highlight the most recent advances in understanding mechanobiology and the interaction between biomechanical properties and the airway epithelium in the pathogenesis of IPF. We seek to describe a positive feedback loop underlying pulmonary fibrosis, in which pro-fibrotic mechanobiological responses of airway epithelial cells drive biomechanical alterations in the lung airways. In parallel, these biomechanical changes further stimulate pro-fibrotic responses in the epithelial cells, perpetuating the cycle. Additionally, we aim to provide a comprehensive perspective on the role of lung biomechanics in the progression of fibrosis, emphasizing the critical need to disrupt this insidious feedback loop to halt or prevent the advancement of lung fibrosis.