CFTR Trafficking And Signaling In Respiratory Epithelium

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CFTR is not a gluten lover either - EMBO Press

function of CFTR without affecting synthesis or trafficking of the protein (Cutting, 2015). The FDA-approved small molecule CFTR potentiator VX-770 (Ivacaftor) is in use to treat patients with CFTR mutations that inhibit channel activity, whereas patients with the DF508 mutation are treated with a combination of VX-770 and the CFTR correc-

Induction of HSP70 promotes ΔF508 CFTR trafficking

native chaperones to interact and keep CFTR on the Original submission in response to a special call for papers on CFTR Trafficking and Signaling in Respiratory Epithelium. Address for reprint requests and other correspondence: P. L. Zeit-lin, Eudowood Division of Pediatric Respiratory Sciences, Johns

Posters - Wiley Online Library

62. f508del cftr mutation affects ciliary structure, junction integrity, and autotaxin-lpa signaling axis in cf airway 1216(16( 9$5,$176 ,1 7+( 5(*,21 7+$7 1$785$//< (6&$3( 10' $5( ,'($/ targets for readthrough and triple combination therapy 64. structural dynamics of cftr channel gating revealed by single-molecule fret 65.

Putting CHIP(s) on the Table: Introducing Nitrosothiols into

Nitric oxide (NO) synthases are abundant in the respiratory epithelium and are essential for the formation of stable bioactive S-nitrosothiols (SNOs), which are important for cellular signaling,-NO transfer, and regulation of protein function (10). Dysregulation of SNO formation is implicated in multiple respiratory diseases (10), including CF.

Viruses in cystic fibrosis patients airways

In CF respiratory epithelium, which is the first barrier against viruses but also where they mainly replicate, impaired innate immune defenses decrease viral clear-ance and increase replication (Colasurdo et al., 2006; Pittet et al., 2010). CFTR gene mutations are numerous and may abolish or reduce CFTR protein functions ( CF-causing

CFTR dysfunction in Cystic Fibrosis and Chronic Obstructive

CFTR are unable to restrict salt absorption through ENaC [10]. Indeed, CFTR and ENaC play the most important roles in maintaining fluid homeostasis by controlling the movement of water through the epithelium, thus regulating the hydration of the epithelial surface in many organs.

15th Scientific Meeting -

in the CFTR gene that severely disrupt CFTR-dependent HCO3- secretion6 , and CFTR mutations that impair the ability of the CFTR channel to switch from a Cl- conductive into a HCO3- conductive mode upon activation of the WNK/SPAK signaling pathway increase the risk for pancreatitits and simusitis7,8. However, in contrast to the wealth of

A Mathematical Model of the Phosphoinositide Pathway

activity of the epithelium sodium channel, ENaC, which is activated by PI(4,5)P 2. Moderating ENaC activity can have a therapeutic effect in Cystic Fibrosis (CF) patients. Our model suggests control strategies where the activities of the enzyme PIP5KI or the PI4K+PIP5KI+DVL protein complex are decreased and cause an efficacious reduction in PI

VIP as a Corrector of CFTR Trafficking and Membrane Stability

Our group has recently demonstrated that VIP regulates CFTR membrane stability via activation of the VPAC1 receptor and the GDi/q signaling cascade in a PKCH-dependent manner. We also found that prolonged VIP exposure can rescue trafficking to the cell membrane and function of 'F508-CFTR channels; the most commonly found mutation in CF.


mutations of CFTR leading to cystic fibrosis either decrease its open probability or compromise its folding and trafficking to the plasma membrane [4]. Established strategies directed towards the treatment of this debilitating disease involve the restoration of the function of CFTR by

Cystic Fibrosis Related Liver Diseases: New Paradigm for

of CFTR affects biliary epithelium innate immunity and causes TLR4-NF-kappaB-mediated inflammatory response in mice. Gastro-enterology 2011;141:1498-1508. 10) Fiorotto R, Villani A, Kourtidis A, Scirpo R, Amenduni M, Geibel PJ, et al. CFTR controls biliary epithelial inflammation and permeability by regulating Src tyrosine kinase activity.


EC Pulmonology and Respiratory Medicine 8.4 (2019): 336-344. The anatomic structure of the lung The lung has three lobes on the right and two on the left. There are the trachea, the branching bronchi, and the lower and terminal bronchioles. The bronchi are lined by columnar epithelium that have mucus secreting glands.

Effects of antibiotics on bronchial epithelial differentiation

activate various pro-inflammatory signaling pathways as well as maintaining the balance of production and clearance of mucus and mucins in the respiratory tract. In addition to producing anti-microbial compounds, the epithelia also produces cytokines, chemokines, lipid

COMMENTARY TGF-β and lung fluid balance in ARDS

Acute respiratory distress syndrome (ARDS) is characterized by hypoxemia from flooding of the distal airspaces of the lung with protein-rich edema fluid. Pulmonary edema develops because of an increase in lung vascular per-meability and from injury to the alveolar epithelium that diminishes the normal ca-pacity of the alveolar epithelium to remove

University of Groningen Intestinal nuclear receptor signaling

Table 1. 16Classification of CFTR mutations. Mutation class Protein defect Example of mutation I. No synthesis G542X II. Defective processing and trafficking F508del III. Defect in channel regulation or gating G551D IV. Decreased channel conductance R117H V. Reduced synthesis or trafficking A455E VI. Decreased stability Q1412X Manifestations of CF

Pro-inflammatory effect of sodium 4-phenylbutyrate in F508

Jun 23, 2008 Cystic Fibrosis (CF) is a lethal disease caused by defective function of the cftr gene product, the CF Transmembrane conductance Regulator (CFTR) that leads to abnormal chloride transport in lung epithelium. The major cause of mortality and morbidity in CF patients is lung disease with the development of a progressive chronic respiratory

CFTR trafficking and signaling in respiratory epithelium

CFTR trafficking and signaling in respiratory epithelium BRUCE R. PITT Department of Environmental and Occupational Health, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15238 RESEARCH IN CYSTIC FIBROSIS (CF) remains at the leading edge of investigations employing human genetics and molecular and cellular


associated to CF illness. The most common CFTR mutation, F508del/F508del, results in a misfolded protein that is improperly glycosylated. The homozygous F508del CFTR protein is degraded into endosomal vesicles failing to reach the apical surface of the epithelium. Other CFTR mutations, such as G551D, form a reduced

CURRICULUM VITAE - University of Pittsburgh

NIH PI ENaC regulation by vesicle trafficking (NIDDK, K99/R00) and recycling 2008-2014 NIH (NIDDK) PI Regulation of ENaC by miRNAs 2010-2012 O Brien Center Pilot NIH (NIDDK) Co-investigator Traffic Regulatory proteins & ENaC 2010-2013 R01-PI R.A. Frizzell

CFTR Correctors and Antioxidants Partially Normalize Lipid

and pro-inflammatory signaling in airway epithelium using mass spectrometric, protein array. We observed a striking imbalance in fatty acid and ceramide metabolism, associated with chronic oxidative stress under basal conditions in CF mouse lung and well-differentiated bronchial epithelial cell cultures of CFTR knock out pig and CF patients.

Pulmonary Research Day Abstract Cover

signaling protein that is responsible for inflammation as well as cell death. It has been suggested that autophagy regulates TNF-mediated cell death in the intestinal epithelium, but only under conditions of infection and damage; thus a direct connection between autophagy and intestinal epithelial cell death is lacking.

Surprises from the Airway Epithelium

to cholinergic stimulation than wild-type trafficking defect in lacri animals. Huang and colleagues (2) de- glands of humans with scribe compartmentalized signaling at the drome, who suffer from apical membrane of airway epithelial cells mouth (7, 8). And what that regulates activity of the cystic fibrosis tions of species differencl

Lindsay R. Stolzenburg and Ann Harris* The role of microRNAs

sis. In chronic respiratory disease, wherein lung func-tion decline results in an inability to breathe, both the pathogenicity and the restorative nature of miRNAs are well studied. More research and better tools, however, are needed to fully understand the functional implications of miRNAs in lung health and disease. In this review, we


55 CFTR contributes to neuronal homeostasis in the olfactory epithelium by regulating the function of microvillar cells: S. Pfister, T. Weber, R. Elsaesser, J.-M. Fritschy, I. Knuesel Group Leader: SHIH-CHII LIU 56 Real-time speaker identification using the AEREAR2 event-based silicon cochlea: C.-H. Li, T. Delbruck, S.-C. Liu

Activation of NF-κB in airway epithelial cells is dependent

lator (CFTR) mutations have many effects on the phys-iology of respiratory epithelial cells in addition to the expected effects on Cl2 transport. One of the major clinical manifestations of CFTR mutations is excessive airway inflammation (14 17), implying that CFTR af-fects the immune function of airway epithelial cells,

Pluripotent stem cells for disease modeling and drug

CFTR is a priority in the field. High throughput (HT) screens have identified CFTR potentiators, which restore the channel activity by enhancing gating [1, 2], and correc-tors, which rescue the most frequent trafficking mutant Correspondence: [email protected] 1Leibniz Research Laboratories for Biotechnology and Artificial Organs


help regulate the gating and trafficking of the channel (6 8). CFTR activation requires PKA-dependent phosphorylation of in respiratory tract epithelium, and

Cystic Fibrosis: Defeated - Normal Breathing: The Key to

In mice subjected to low oxygen in vivo, CFTR mRNA expression in airways, gastrointestinal tissues, and liver was repressed. CFTR mRNA expression was also diminished in pulmonary tissues taken from hypoxemic subjects at the time of lung transplantation. Environmental factors that induce hypoxic signaling regulate CFTR mRNA and epithelial Cl(-)

Comparative analyses of long non - Respiratory Research

the CFTR gene. CF mutations, of which the most common is F508del-CFTR, prevents correct folding, trafficking and function of the mutant CFTR protein and is further manifested by the hyper-expression of pro-inflammatory cytokines and chemokines into the airway lumen leading to bronchiectasis and culminating in lung destruction.


promotes CFTR maturation and trafficking in MDCK monolayers (Bebök et al, 2001). In their abstract, the researchers wrote, Together, our data indicate that improved cellular oxygenation can increase endogenous CFTR maturation and/or trafficking Another group of US scientists from Alabama (Department of Genetics, Fleming James Cystic

Pharmacological and genetic approaches determine protease and

epithelium. Rabbit polyclonal beta-ENaC antibody was used as a primary antibody to detect human 3-ENaC protein in the small airway epithelium. A) A whole small airway from a GOLD 2 patient showing beta-ENaC protein staining in purple with the epithelium staining green. B) The closer view of the boxed region on A with the

Surprises from the airway epithelium

The epithelium of the pulmonary air-ways subserves a wide range of func-tions, from providing a barrier against inhaled particles and pathogens to trans-mitting signals to subepithelial cells. Given the central place of the epithelium in respiratory tract pathophysiology, the molecular determinants of epithelial func-

A Pseudomonas aeruginosa Toxin that Hijacks the Host

CFTR from endosomes that recycle to the plasma membrane to a degradative pathway. To investigate further the trafficking of CFTR in the presence of Cif, we followed the movement of CFTR through intracellular compartments via differential centrifugation and Optiprep gradi-ent fractionation. In these experiments, apical membrane CFTR

ResearchIncreased plasma membrane - Respiratory Research

CFTR mice. Other studies demonstrate the relationship between membrane cholesterol and CFTR by examining restoration of wt CFTR in CF epithelial cells and examin-ing the impact of acute CFTR inhibition. Methods Cell culture Human epithelium 9/HTEo-cells over expressing the CFTR R domain (pCEPR) and mock-transfected 9/