Epithelial Injury and Dysfunction in the Pathogenesis of Idiopathic Pulmonary Fibrosis

摘要

Idiopathic pulmonary fibrosis is a disease of older adults leading to progressive dyspnea and reduced exercise capacity, typically resulting in death within 3-5 years of diagnosis. Underlying genetic susceptibility combined with environmental insults is proposed to trigger a chronic wound repair response, leading to activation of the fibrotic cascade. Perturbations in several molecular pathways mediate vulnerability of the alveolar epithelium to injurious agents, including the unfolded protein response, autophagy, mitophagy, and cellular senescence. These cellular responses are intricately intertwined and link genetic susceptibility to the progressive fibrotic phenotype. Ongoing studies investigating these pathways in type II alveolar epithelial cells show promise for identifying new targeted interventions that could prevent or halt the progression of IPF.