CFTR Involvement in Cell Migration and Epithelial Restitution

Abstract

Over the past decade, research has shown that cystic fibrosis transmembrane conductance regulator (CFTR) plays an important role in epithelial cell migration and wound healing. Experiments with airway epithelium, ovarian epithelial cells, placental epithelium and epidermal keratinocytes demonstrated that CFTR function is necessary to achieve maximum migration rates during restitution and in certain cancer cells, CFTR activity contributes to tumor cell invasion. Multiple mechanisms appear to underlie the motility-promoting actions of CFTR, and although many details remain to be established, our present understanding indicates that processes such as electrotaxis (galvanotaxis), integrin-mediated cell adhesion and lamellipodia protrusion are dependent on normal CFTR function. In this chapter, the role of CFTR in epithelial cell migration and its implications in cystic fibrosis (CF) will be reviewed with emphasis on the underlying mechanisms that may explain observations made in various epithelial tissues, particularly in airways. Ultimately, a better understanding of CFTR involvement in epithelial repair may lead to new therapeutic approaches to improve barrier function and reduce airway infection and inflammation associated with CF.

Transcriptomic analysis of CFTR-impaired endothelial cells reveals a pro-inflammatory phenotype

“…We also obtained evidence that CFTR is expressed at the lamellipodia of migrating ECs and therefore is possibly involved in EC polarization and migration. Our findings are consistent with reports that CFTR regulates lamellipodia protrusion and cell migration in non-EC types 82,83 . It is becoming increasingly obvious that CFTR regulates cell migration across a diverse range of cell types, however the underlying mechanisms remain to be further uncovered, since delayed wound repair may augment inflammation in CF 82 .…”