Cystic fibrosis transmembrane conductance regulator (CFTR) and autophagy: hereditary defects in cystic fibrosis versus gluten-mediated inhibition in celiac disease.

Cystic fibrosis transmembrane conductance regulator (CFTR) and autophagy: hereditary defects in cystic fibrosis versus gluten-mediated inhibition in celiac disease. Oncotarget. 2019 Jul 08;10(43):4492-4500 Authors: Maiuri L, Raia V, Piacentini M, Tosco A, Villella VR, Kroemer G Abstract Cystic Fibrosis (CF) is the most frequent lethal monogenetic disease affecting humans. CF is characterized by mutations in cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel whose malfunction triggers the activation of transglutaminase-2 (TGM2), as well as the inactivation of the Beclin-1 (BECN1) complex resulting in disabled autophagy. CFTR inhibition, TGM2 activation and BECN1 sequestration engage in an 'infernal trio' that locks the cell in a pro-inflammatory state through anti-homeostatic feedforward loops. Thus, stimulation of CFTR function, TGM2 inhibition and autophagy stimulation can be used to treat CF patients. Several studies indicate that patients with CF have a higher incidence of celiac disease (CD) and that mice bearing genetically determined CFTR defects are particularly sensitive to the enteropathogenic effects of the orally supplied gliadin (a gluten-derived protein). A gluten/gliadin-derived peptide (P31-43) inhibits CFTR in mouse intestinal epithelial cells, causing a local stress response that contributes to the immunopathology of CD. In particular, P31-43-induced CFTR inhibition elicits an epithelial s...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research