Pathophysiology of Lung Disease and Wound Repair in Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive, life-threatening condition affecting many organs and tissues, the lung disease being the chief cause of morbidity and mortality. Mutations affecting the CF Transmembrane Conductance Regulator (CFTR) gene determine the expression of a dysfunctional protein that, in turn, triggers a pathophysiological cascade, leading to airway epithelium injury and remodeling. In vitro and in vivo studies point to a dysregulated regeneration and wound repair in CF airways, to be traced back to epithelial CFTR lack/dysfunction. Subsequent altered ion/fluid fluxes and/or signaling result in reduced cell migration and proliferation. Furthermore, the epithelial-mesenchymal transition appears to be partially triggered in CF, contributing to wound closure alteration. Finally, we pose our attention to diverse approaches to tackle this defect, discussing the therapeutic role of protease inhibitors, CFTR modulators and mesenchymal stem cells. Although the pathophysiology of wound repair in CF has been disclosed in some mechanisms, further studies are warranted to understand the cellular and molecular events in more details and to better address therapeutic interventions.

Automated summary

Cystic fibrosis is an autosomal recessive genetic disease that mainly affects the lungs, leading to airway injury and remodeling due to mutations in the CFTR gene. Dysregulated regeneration and wound repair in CF airways, as well as altered epithelial-mesenchymal transition contributing to wound closure alteration, have been identified in in vitro and in vivo studies. Therapeutic approaches such as protease inhibitors, CFTR modulators, and mesenchymal stem cells show promise in addressing this defect, but further research is needed for a better understanding of cellular and molecular events in wound repair in CF.