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.
Conflict of Interest Statement: The authors have no conflict of interest to declare.
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Acknowledgments
Our research was supported by the Hungarian Scientific Research Fund (PD115974 (JM), K116634 (PH), NF101116 (ZR)); the Momentum Grant of the Hungarian Academy of Sciences (LP2014-10/2014); the Cystic Fibrosis Canada (GL), NIH R01-DK75302 (GL); and the Canadian Institute of Health Research (GL), the NIH DK096327 (AU), NIH DK097820 (AU), NIH DK096518 (JE), Cystic Fibrosis Trust (UK) INOVCF- SRC003 (MAG), National Pancreas Foundation Grant (AU), NIH/NIDCR intramural grant DE000735 (SM), NIH R01-DK058088 (MST), and GL is a recipient of a Canada Research Chair.
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Hegyi, P. et al. (2016). CFTR: A New Horizon in the Pathomechanism and Treatment of Pancreatitis. In: Nilius, B., de Tombe, P., Gudermann, T., Jahn, R., Lill, R., Petersen, O. (eds) Reviews of Physiology, Biochemistry and Pharmacology Vol. 170. Reviews of Physiology, Biochemistry and Pharmacology, vol 170. Springer, Cham. https://doi.org/10.1007/112_2015_5002
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