scholarly journals TALENs Facilitate Single-step Seamless SDF Correction of F508del CFTR in Airway Epithelial Submucosal Gland Cell-derived CF-iPSCs

2016 ◽  
Vol 5 ◽  
pp. e273 ◽  
Author(s):  
Shingo Suzuki ◽  
R Geoffrey Sargent ◽  
Beate Illek ◽  
Horst Fischer ◽  
Alaleh Esmaeili-Shandiz ◽  
...  
Keyword(s):  
Gland Cell ◽  
Single Step ◽  
Airway Epithelial ◽  
Submucosal Gland

scholarly journals Characterization of Novel Airway Submucosal Gland Cell Models for Cystic Fibrosis

2005 ◽  
Vol 15 (6) ◽  
pp. 251-262 ◽  
Author(s):  
Ana da Paula ◽  
Anabela Ramalho ◽  
Carlos Farinha ◽  
Judy Cheung ◽  
Rosalie Maurisse ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Gland Cell ◽  
Cell Models ◽  
Submucosal Gland

scholarly journals Genome-Wide RNAi Screening Identifies Novel Pathways/Genes Involved in Oxidative Stress and Repurposable Drugs to Preserve Cystic Fibrosis Airway Epithelial Cell Integrity

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1936
Author(s):  
Javier Checa ◽  
Itziar Martínez-González ◽  
Maria Maqueda ◽  
Jose Luis Mosquera ◽  
Josep M. Aran
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Stress Resistance ◽  
Local Similarity ◽  
Airway Epithelial ◽  
Cell Integrity ◽  
Submucosal Gland ◽  
Oxidative Stress Resistance ◽  
Gland Cells ◽  
Genome Wide

Recurrent infection-inflammation cycles in cystic fibrosis (CF) patients generate a highly oxidative environment, leading to progressive destruction of the airway epithelia. The identification of novel modifier genes involved in oxidative stress susceptibility in the CF airways might contribute to devise new therapeutic approaches. We performed an unbiased genome-wide RNAi screen using a randomized siRNA library to identify oxidative stress modulators in CF airway epithelial cells. We monitored changes in cell viability after a lethal dose of hydrogen peroxide. Local similarity and protein-protein interaction network analyses uncovered siRNA target genes/pathways involved in oxidative stress. Further mining against public drug databases allowed identifying and validating commercially available drugs conferring oxidative stress resistance. Accordingly, a catalog of 167 siRNAs able to confer oxidative stress resistance in CF submucosal gland cells targeted 444 host genes and multiple circuitries involved in oxidative stress. The most significant processes were related to alternative splicing and cell communication, motility, and remodeling (impacting cilia structure/function, and cell guidance complexes). Other relevant pathways included DNA repair and PI3K/AKT/mTOR signaling. The mTOR inhibitor everolimus, the α1-adrenergic receptor antagonist doxazosin, and the Syk inhibitor fostamatinib significantly increased the viability of CF submucosal gland cells under strong oxidative stress pressure. Thus, novel therapeutic strategies to preserve airway cell integrity from the harsh oxidative milieu of CF airways could stem from a deep understanding of the complex consequences of oxidative stress at the molecular level, followed by a rational repurposing of existing “protective” drugs. This approach could also prove useful to other respiratory pathologies.

scholarly journals Expression of the chloride channel CLC-K in human airway epithelial cells

2005 ◽  
Vol 83 (12) ◽  
pp. 1123-1128 ◽  
Author(s):  
Jennifer L. Mummery ◽  
Jennifer Killey ◽  
Paul Linsdell
Keyword(s):  
Cystic Fibrosis ◽  
Chloride Channel ◽  
Chloride Channels ◽  
Human Cell Line ◽  
Genetic Mutation ◽  
Airway Epithelial Cells ◽  
K Channel ◽  
Airway Epithelial ◽  
Submucosal Gland ◽  
Patch Clamp Recording

Airway submucosal gland function is severely disrupted in cystic fibrosis (CF), as a result of genetic mutation of the cystic fibrosis transmembrane conductance regulator (CFTR), an apical membrane Cl– channel. To identify other Cl– channel types that could potentially substitute for lost CFTR function in these cells, we investigated the functional and molecular expression of Cl– channels in Calu-3 cells, a human cell line model of the submucosal gland serous cell. Whole cell patch clamp recording from these cells identified outwardly rectified, pH- and calcium-sensitive Cl– currents that resemble those previously ascribed to ClC-K type chloride channels. Using reverse transcription – polymerase chain reaction, we identified expression of mRNA for ClC-2, ClC-3, ClC-4, ClC-5, ClC-6, ClC-7, ClC-Ka, and ClC-Kb, as well as the common ClC-K channel β subunit barttin. Western blotting confirmed that Calu-3 cells express both ClC-K and barttin protein. Thus, Calu-3 cells express multiple members of the ClC family of Cl– channels that, if also expressed in native submucosal gland serous cells within the CF lung, could perhaps act to partially substitute lost CFTR function. Furthermore, this work represents the first evidence for functional ClC-K chloride channel expression within the lung.

Acetylcholine-stimulated chloride flux in tracheal submucosal gland cells

1988 ◽  
Vol 65 (4) ◽  
pp. 1891-1894 ◽  
Author(s):  
C. M. Yang ◽  
J. M. Farley ◽  
T. M. Dwyer
Keyword(s):  
Gland Cell ◽  
Equilibrium Concentration ◽  
Acetylcholinesterase Activity ◽  
Effective Concentration ◽  
Submucosal Gland ◽  
Chloride Flux ◽  
Gland Cells ◽  
Glycoprotein Secretion ◽  
Electrochemical Equilibrium

The Cl content of isolated tracheal submucosal gland cells was studied using 36Cl as a tracer. 36Cl uptake reached a steady state within 10 min, yielding an estimate of intracellular Cl concentration of approximately 40 mM. Intracellular Cl fell rapidly when ouabain or furosemide was added, indicating that isolated tracheal submucosal gland cells concentrate Cl above its electrochemical equilibrium concentration. Acetylcholine (ACh) caused a Ca2+-dependent decline in cell Cl, with an effective concentration for a 50% response (EC50) of 62 nM; this loss of cell Cl was blocked by atropine or pirenzepine. The EC50 was 6 nM in cells when 95% of the acetylcholinesterase activity was abolished by diisopropylfluorophosphate (DFP) treatment. ACh continued to cause a decline in cell Cl even after a 7-day course of DFP treatment, which has been shown to abolish ACh-stimulated mucous glycoprotein secretion (23). After the 7-day course of DFP treatment, the EC50 for ACh increased to 77 nM. Thus the Cl economy of the tracheal submucosal gland cell resembles that of cells in epithelia that secrete fluid; in addition, the transmitter-dependent loss of cell Cl is under long-term metabolic control of the cell.

New Ultrastructural Observations on Injury and Regeneration of Cilia in Mammalian Conducting Airway Epithelium

1981 ◽  
Vol 39 ◽  
pp. 624-625
Author(s):  
J.L. Carson ◽  
A.M. Collier
Keyword(s):  
Respiratory Tract ◽  
Airway Epithelium ◽  
Defense Mechanisms ◽  
Normal Growth ◽  
Fetal Lung ◽  
Secretory Cells ◽  
Airway Epithelial ◽  
Ciliated Cells ◽  
Conducting Airway ◽  
Conducting Airways

The ciliated cells lining the conducting airways of mammals are integral to the defense mechanisms of the respiratory tract, functioning in coordination with secretory cells in the removal of inhaled and cellular debris. The effects of various infectious and toxic agents on the structure and function of airway epithelial cell cilia have been studied in our laboratory, both of which have been shown to affect ciliary ultrastructure.These observations have led to questions about ciliary regeneration as well as the possible induction of ciliogenesis in response to cellular injury. Classical models of ciliogenesis in the conducting airway epithelium of the mammalian respiratory tract have been based primarily on observations of the developing fetal lung. These observations provide a plausible explanation for the embryological generation of ciliary beds lining the conducting airways but do little to account for subsequent differentiation of ciliated cells and ciliogenesis during normal growth and development.

V884: Demonstration of a Novel Single-Step Percutaneous Access Sheath for Nephrostolithotomy: A Video Presentation

2005 ◽  
Vol 173 (4S) ◽  
pp. 240-240
Author(s):  
Premal J. Desai ◽  
David A. Hadley ◽  
Lincoln J. Maynes ◽  
D. Duane Baldwin
Keyword(s):  
Single Step ◽  
Video Presentation ◽  
Percutaneous Access ◽  
Access Sheath

Generation of Clara cells from murine pluripotent stem cells – a new tool to explore airway epithelial regeneration

Pneumologie ◽  
2014 ◽  
Vol 68 (06) ◽  
Author(s):  
K Katsirntaki ◽  
C Mauritz ◽  
S Schmeckebier ◽  
M Sgodda ◽  
V Puppe ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Airway Epithelial ◽  
Clara Cells ◽  
Epithelial Regeneration
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