Disease relevance of Cftr

• Estrogen-induced abnormally high cystic fibrosis transmembrane conductance regulator expression results in ovarian hyperstimulation syndrome [1].
• Phylogenetic analysis of cystic fibrosis transmembrane conductance regulator gene in mammalian species argues for the development of a rabbit model for cystic fibrosis [2].
• Due to its existence and multifunction in biliary epithelial, over- or less-expression of CFTR in the liver may play an important role in the development of CF liver disease (CFLD) [3].
• Postmeiotic expression is maximal in the round spermatids of stages VII and VIII, suggesting that CFTR plays a critical role in spermatogenesis and that deficiency of this function contributes to CF male infertility [4].
• Gene transfer efficiency was compared using direct injection of an adenovirus vector encoding for the marker gene beta-galactosidase (beta-gal), a control adenovirus vector encoding for the cystic fibrosis transmembrane conductance regulator gene, a plasmid encoding for beta-gal, or a control plasmid [5].

High impact information on Cftr

• Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) [4].
• In the testis, CFTR expression is regulated during the cycle of the seminiferous epithelium [4].
• Determination of CFTR messenger RNA in rat tissues by in situ hybridization shows that it is specifically expressed in the ductal cells of the pancreas and the salivary glands [4].
• In support of these data P2Y(6) receptor stimulation differentially activates CFTR in Xenopus oocytes [6].
• These findings suggest that Ca(2+)- and cAMP-regulated Cl- channels may participate in control of fluid and electrolyte secretion by intrahepatic bile duct epithelial cells, and that the cAMP-regulated conductance is associated with endogenous expression of CFTR [7].

Chemical compound and disease context of Cftr

• INTRODUCTION: Guanylin and uroguanylin are intestinal or urine peptides that stimulate epithelial electrolyte/fluid secretion by activating the cystic fibrosis gene product (CFTR) [8].
• This domain directly interacted with syntaxin 1A, a SNARE protein involved in both neurotransmitter release and modulation of calcium channels and cystic fibrosis transmembrane regulator (CFTR) chloride channels [9].
• A molecular mechanism for aberrant CFTR-dependent HCO(3)(-) transport in cystic fibrosis [10].
• ATP acting on both cell types activated at least two channels, the Ca2+-activated Cl- channel and a Ca2+-independent glibenclamide-sensitive Cl--current, possibly cystic fibrosis transmembrane regulator (CFTR) [11].
• The flavonoid genistein and the benzo[c]quinolizinium MPB-07 have been shown to activate the cystic fibrosis transmembrane conductance regulator (CFTR), the protein that is defective in cystic fibrosis [12].

Biological context of Cftr

• It is unknown whether cGMP signaling or phosphorylation regulates the insertion of CFTR associated vesicles from the cytoplasm to the surface of enterocytes [13].
• To gain insights into the regulation of the mouse and rat cystic fibrosis transmembrane conductance regulator (CFTR) genes, we cloned and sequenced their respective upstream promoter regions [14].
• Transfection of mouse promoter deletional constructs into expressing and non-expressing CFTR murine cell lines revealed that the Pu.Py stretch and the Y-box act, respectively, as negative and positive elements of basal transcription that confer no apparent tissue specificity [14].
• Regulation of the cystic fibrosis transmembrane conductance regulator channel by beta-adrenergic agonists and vasoactive intestinal peptide in rat smooth muscle cells and its role in vasorelaxation [15].
• Our results indicate that 50-250 of functional CFTR Cl(-) channels occur in adult alveolar cells and could contribute to alveolar liquid homeostasis [16].

Anatomical context of Cftr

• We conclude that cAMP and cGMP-dependent phosphorylation regulates fluid secretion and CFTR trafficking to the surface of enterocytes in rat jejunum [13].
• Reciprocal protein kinase A regulatory interactions between cystic fibrosis transmembrane conductance regulator and Na+/H+ exchanger isoform 3 in a renal polarized epithelial cell model [17].
• Here we show expression of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel in rat aortic smooth muscle cells [15].
• The aim of current study is to investigate the expression of CFTR in the liver of common bile duct ligated (BDL) rats [3].
• Recent studies have implicated the CFTR in fluid transport by the adult alveolar epithelium, but its presence has not been demonstrated directly [16].

Associations of Cftr with chemical compounds

• Glibenclamide, unlike secretin and forskolin, was able to stimulate secretion in Cftr tm1Unc mice, thus indicating that this secretory mechanism was preserved [18].
• Upon ovarian hyperstimulation, rats develop OHSS symptoms, with up-regulated CFTR expression and enhanced CFTR channel activity, which can also be mimicked by administration of estrogen, but not progesterone, alone in ovariectomized rats [1].
• Administration of progesterone that suppresses CFTR expression or antiserum against CFTR to OHSS animals results in alleviation of the symptoms [1].
• Whether CFTR is present in vesicular compartments within chloride secretory cells in the intestine is unknown and the role of cAMP-dependent vesicle insertion in regulating CFTR and intestinal fluid secretion remains unclear [19].
• The guanylin/uroguanylin receptor GC-C, cGKII, CFTR, and AE2 were all found in the same segments of the ductal system, where they were confined to the apical membrane of centroacinar cells and proximal duct epithelial cells, a circumstance suggesting that both peptides may act through the ductal lumen [8].

Regulatory relationships of Cftr

• The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-activated chloride channel critical to intestinal anion secretion [19].
• Secretin stimulates ductular cystic fibrosis transmembrane conductance regulator (CFTR)-dependent Cl- efflux and subsequent biliary HCO3- secretion, possibly via Cl-/HCO3- anion exchange (AE) [20].

Other interactions of Cftr

• Shank2-CFTR interaction was verified by co-immunoprecipitation experiments in mammalian cells [21].
• Binding to GC-C results in generation of cGMP, activation of type II cGMP-dependent protein kinase, phosphorylation of CFTR and increased chloride and bicarbonate secretion [22].
• Using RT-PCR, Western blot, and electrophysiological techniques we show that cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel expressed in many epithelia, is involved in the pathogenesis of OHSS [1].
• ATP-regulated (K(ATP)) channels are formed by an inward rectifier pore-forming subunit (Kir) and a sulfonylurea (glibenclamide)-binding protein, a member of the ATP binding cassette family (sulfonylurea receptor (SUR) or cystic fibrosis transmembrane conductance regulator) [23].
• CONCLUSIONS: These results suggest that increases in the osmotic water permeability due to the expression of AQP2 are critical for a rapid activation of regulatory volume decrease mechanisms, which would be linked to cystic fibrosis transmembrane conductance regulator and to barium-sensitive potassium channels [24].

Analytical, diagnostic and therapeutic context of Cftr

• Shank2, one of these scaffolding proteins, showed a strong interaction with CFTR by yeast two-hybrid assays [21].
• The species-specific pattern of cystic fibrosis transmembrane conductance regulator (CFTR) expression was investigated in order to identify species closely related to man which can be used as potential cystic fibrosis (CF) animal models [2].
• Increased expression of cystic fibrosis transmembrane conductance regulator in rat liver after common bile duct ligation [3].
• The CFTR was also found at the protein level in Western blot experiments employing lysates of freshly isolated alveolar cells [16].
• CFTR mRNA was detected by semiquantitative polymerase chain reaction on the day of cell isolation but was rapidly reduced by 60% after 24 h of cell culture [16].

References