Cystic Fibrosis Transmembrane Conductance Regulators (CFTR)

Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and chloride channel in vertebrates. Cystic Fibrosis (CF) remains one of the most common life-shortening genetic diseases affecting the lung and other organs which is caused by mutations in the gene CFTR. CFTR functions as a cyclic adenosine monophosphate-dependent anion channel that transports Cl^- and HCO3^- across epithelial surfaces, and disruption of these ion transport processes plays a central role in the pathogenesis of CF. These findings provided the rationale for pharmacologic modulation of ion transport, either by targeting mutant CFTR or alternative ion channels that can compensate for CFTR dysfunction, as a promising therapeutic approach. High-throughput screening has supported the development of CFTR modulator compounds.

Creative Bioarray offers assays to test effects of lead compounds on CFTR function in epithelia, such as Cl^- and HCO3^- secretions from primary human epithelial cells, small intestinal and colonic epithelia of animals.

Fig. 1 Junchoto (JCT)-induced CFTR currents in HEK293T cells transiently transfected with CFTR

CFTR Assay

CFTR channels are involved in numerous epithelial cell functions, such as regulation of pH_i and cell volume, mucus secretion and expansion, development and growth. CFTR channels have been well recognized as therapeutic targets for treating CF and other diseases. Utilizing digital cell imaging with novel fluorescent dye in epithelial cell lines overly expressing CFTR, Creative Bioarray offers assays to test effects of lead compounds on CFTR activity in both epithelial cell lines and primary human epithelial cells.

Fig. 2 ACC assay correlates with Ussing chamber measurements of patient-specific responses to interventions in primary nasal epithelial cultures

References

1. Numata T, et al. Cellular mechanism for herbal medicine Junchoto to facilitate intestinal Cl/water secretion that involves cAMP-dependent activation of CFTR. J. Nat. Med. 2018; 72: 694–705.

2. Ahmadi S, et al. Phenotypic profiling of CFTR modulators in patient-derived respiratory epithelia. Genomic Med. 2017; 2:12

Related Section

• Calcium Channels
• Potassium Channels
• 5-HT3 receptors
• ATP gated P2X Channels
• AISCs