Elastic Fibers in the Pathogenesis of Cystic Fibrosis: Mechanisms, Consequences, and Therapeutic Implications

Abstract

Cystic fibrosis (CF) is a multisystem autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, affecting approximately 100,000 individuals worldwide. While the primary pathology of CF has historically been framed around airway mucus obstruction, chronic infection, and neutrophilic inflammation, emerging evidence points to profound remodeling of the extracellular matrix (ECM), and elastic fibers in particular, as central contributors to disease progression. Elastic fibers, composed of an elastin core surrounded by a fibrillin-rich microfibril scaffold, provide tissues with the resilience and recoil necessary for repetitive mechanical deformation, properties especially critical in the lung, large airways, skin, and vasculature. In CF, a convergence of proteolytic imbalance, oxidative stress, inflammatory mediators, and impaired CFTR-dependent ion transport conspires to degrade and destabilize these fibers at multiple anatomical sites. The consequences include progressive airflow obstruction, bronchiectasis, emphysema-like changes, impaired mucociliary clearance, and systemic connective tissue vulnerabilities. This paper provides a detailed review of elastic fiber biology, the mechanisms by which CF pathophysiology disrupts elastic fiber integrity, the downstream structural and functional consequences, and potential therapeutic avenues targeting elastic fiber preservation or restoration.