THE ROLE OF THE ENDOTHELIUM IN CYSTIC FIBROSIS ASSOCIATED LIVER DISEASE

Cystic fibrosis (CF) is an autosomal recessive disorder most frequently observed in the Caucasian population with an annual incidence of 1 in 3000 live births. CF is a multisystem disease primordially affecting the lungs but also the pancreas, intestines, liver, vas deferens and sweat glands. It results from loss of function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR gene encodes a chloride channel located at the plasma membrane and its defect results in reduced chloride transport. Cystic Fibrosis Liver Disease (CFLD) is the third most frequent cause of death of CF patients, after the pulmonary disease and transplant related complications and develops approximately in 30% of the CF patients. The diagnosis of CFLD is still not clearly defined. Moreover, at the moment it is still unknown why some CF patients suffer from liver disease and this hampers the development of an effective treatment. Recent clinical research from Witters et al. showed that endothelial cells (ECs), the cells that form the inner lining of blood vessels, are of great importance in CFLD. Unfortunately, there are only a handful of studies describing endothelial cells in CF patients. Therefore I will use genetic silencing, expression profiling and metabolic & functional assays in in vitro, in vivo and ex vivo models to unravel the role of CFTR dysfunction in ECs and to explore which roles ECs play in CF and more specifically in CFLD.

Jaar van publicatie:2021

Toegankelijkheid:Open