title: Hyperacidification in cystic fibrosis: links with lung disease and new prospects for treatment.
abstract: A new link between the genetic defect and lung pathology in cystic fibrosis (CF) has been established by the recent discovery of an abnormally acidic pH in the organelles of CF respiratory epithelial cells, along with an increased acidity of the CF airway surface liquid. The defect in cystic fibrosis transmembrane resistance regulator (CFTR) results in hyperacidification of the trans-Golgi network, an organelle responsible for glycosylation, and protein- and membrane-sorting in mammalian cells. Hyperacidification and altered surface glycoconjugates might contribute to mucus thickening, bacterial adhesion and colonization, inflammation, and irreversible tissue damage. The increased acidity of the intracellular organelles and of the lung lining in CF could be linked, and both represent potential therapeutic targets.
authors.affiliation: Dept of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
authors.forename: Jens
authors.initials: J
authors.lastname: Poschet
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Perkett
authors.forename: Vojo
authors.initials: V
authors.lastname: Deretic
mesh_terms: D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D004358:Drug Therapy / Q000639:trends; D006031:Glycosylation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009297:Nasal Mucosa / Q000378:metabolism*; D012141:Respiratory Tract Infections / Q000209:etiology
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator