The CFTR and EGFR relationship in airway vascular growth, and its importance in cystic fibrosis

Abstract

In this issue of the European Respiratory Journal , Martin et al. [1] focus on the life-threatening complication of haemoptysis in cystic fibrosis (CF). The authors examine the role of vascular endothelial growth factor (VEGF)-A on angiogenesis in the normal state and in CF. They report that CF airways at transplantation show increased vascularity and increased VEGF-A expression. In normal human airway epithelial cells they report that VEGF-A synthesis is produced via activation of the epidermal growth factor receptor (EGFR) and is suppressed by a selective EGFR inhibitor. Most novel and exciting are the findings that in airway epithelial cells containing cystic fibrosis transmembrane conductance regulator (CFTR), inhibition of CFTR increases EGFR activation and that an inhibitor of EGFR activation prevents the VEGF-A synthesis induced by suppression of CFTR, suggesting that there is a reciprocal relationship between CFTR and EGFR. Both CFTR and EGFR coexist on the airway epithelial surface. EGFR activation results in “pro-inflammatory responses”; in addition to VEGF-A, this includes other products such as interleukin-8 (a potent neutrophil chemoattractant) [2] and mucins [3]. The fact that inhibition of CFTR results in exaggerated production of VEGF-A suggests that CFTR normally suppresses the EGFR “inflammatory” responses. VEGF-A production occurs in response to EGFR activation. The study by Martin et al. [1] found that suppression of CFTR increased EGFR activation, but only after …