Cystic fibrosis: An inherited disease affecting mucin-producing organs

Abstract

Our current understanding of cystic fibrosis (CF) has revealed that the biophysical properties of mucus play a considerable role in the pathogenesis of the disease in view of the fact that most mucus-producing organs are affected in CF patients. In this review, we discuss the potential causal relationship between altered cystic fibrosis transmembrane conductance regulator (CFTR) function and the production of mucus with abnormal biophysical properties in the intestine and lungs, highlighting what has been learned from cell cultures and animal models that mimic CF pathogenesis. A similar cascade of events, including mucus obstruction, infection and inflammation, is common to all epithelia affected by impaired surface hydration. Hence, the main structural components of mucus, namely the polymeric, gel-forming mucins, are critical to the onset of the disease. Defective CFTR leads to epithelial surface dehydration, altered pH/electrolyte composition and mucin concentration. Further, it can influence mucin transition from the intracellular to extracellular environment, potentially resulting in aberrant mucus gel formation. While defective HCO3− production has long been identified as a feature of CF, it has only recently been considered as a key player in the transition phase of mucins. We conclude by examining the influence of mucins on the biophysical properties of CF sputum and discuss existing and novel therapies aimed at removing mucus from the lungs.

Cilia Dysfunction in Lung Disease

“…The disorder predominantly affects Caucasians with an incidence of 1 in 2500 newborns of Northern European descent (76). Nearly 2000 CFTR mutations have been identified (76, 77).…”

“…The disorder predominantly affects Caucasians with an incidence of 1 in 2500 newborns of Northern European descent (76). Nearly 2000 CFTR mutations have been identified (76, 77). Although affected infants are born with seemingly normal lungs, chronic lung disease develops as a result of abnormal mucociliary clearance, leading to repeated infections and the development of bronchiectasis (78).…”

“…The CFTR gene encodes a cAMP-regulated chloride channel expressed apically in epithelial cells (76). The channel modulates chloride secretion and also regulates other membrane proteins including the epithelial sodium channel (ENaC) (76).…”

“…The channel modulates chloride secretion and also regulates other membrane proteins including the epithelial sodium channel (ENaC) (76). Because both CFTR and ENaC control water movement through the epithelium, CFTR dysfunction leads to increased fluid absorption, dehydration of the epithelial surface, and altered mucin concentration in abnormal airway mucus (76, 79).…”

Les enjeux de la médecine personnalisée appliquée à la mucoviscidose

“…L'altération du transport électrolytique concerne toutes les glandes exocrines de l'organisme, glandes séreuses et à sécrétion de mucus [9,11]. Le dysfonctionnement de la protéine CFTR conduit à un défaut d'hydratation des sécrétions qui deviennent visqueuses et collantes.…”