CFTR: A New Horizon in the Pathomechanism and Treatment of Pancreatitis

Rev Physiol Biochem Pharmacol. 2016:170:37-66. doi: 10.1007/112_2015_5002.

Abstract

Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel that conducts chloride and bicarbonate ions across epithelial cell membranes. Mutations in the CFTR gene diminish the ion channel function and lead to impaired epithelial fluid transport in multiple organs such as the lung and the pancreas resulting in cystic fibrosis. Heterozygous carriers of CFTR mutations do not develop cystic fibrosis but exhibit increased risk for pancreatitis and associated pancreatic damage characterized by elevated mucus levels, fibrosis, and cyst formation. Importantly, recent studies demonstrated that pancreatitis causing insults, such as alcohol, smoking, or bile acids, strongly inhibit CFTR function. Furthermore, human studies showed reduced levels of CFTR expression and function in all forms of pancreatitis. These findings indicate that impairment of CFTR is critical in the development of pancreatitis; therefore, correcting CFTR function could be the first specific therapy in pancreatitis. In this review, we summarize recent advances in the field and discuss new possibilities for the treatment of pancreatitis.

Keywords: CFTR; Cystic fibrosis; Epithelial transport; Pancreas; Pancreatitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Humans
  • Pancreatitis / genetics
  • Pancreatitis / metabolism*

Substances

  • Cystic Fibrosis Transmembrane Conductance Regulator