scholarly journals Cystic fibrosis-related diabetes: an update

QJM ◽  
2020 ◽  
Author(s):  
F Frost ◽  
M J Walshaw ◽  
D Nazareth
Keyword(s):  
Cystic Fibrosis ◽  
Life Expectancy ◽  
Early Mortality ◽  
Transmembrane Conductance Regulator ◽  
Regulator Gene ◽  
Transmembrane Conductance ◽  
Common Life ◽  
Life Threatening ◽  
Underlying Mechanisms ◽  
Cf Transmembrane Conductance Regulator

Summary Cystic fibrosis (CF) is the most common life-threatening inherited condition in the Caucasian population, where mutations in the CF transmembrane conductance regulator gene result in a multifactorial syndrome, with pulmonary disease representing the largest contributor to morbidity and mortality. Life expectancy has improved and the recent development of disease-modifying CF transmembrane conductance regulator modulator therapies is likely to further improve survival. However, increasing life expectancy brings new challenges related to the complications of a chronic disease including an increasing prevalence of CF-related diabetes, itself associated with increased morbidity and early mortality. This review provides an update as regards the underlying mechanisms, investigation and management of CF-related diabetes.

scholarly journals IL-6 and IL-8 increase the expression of glycosyltransferases and sulfotransferases involved in the biosynthesis of sialylated and/or sulfated Lewisx epitopes in the human bronchial mucosa

2008 ◽  
Vol 410 (1) ◽  
pp. 213-223 ◽  
Author(s):  
Sophie Groux-Degroote ◽  
Marie-Ange Krzewinski-Recchi ◽  
Aurélie Cazet ◽  
Audrey Vincent ◽  
Sylvain Lehoux ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cystic Fibrosis ◽  
Early Death ◽  
High Molecular Mass ◽  
Transmembrane Conductance Regulator ◽  
Regulator Gene ◽  
Bronchial Mucosa ◽  
Sialyl Lewisx ◽  
Transmembrane Conductance ◽  
Cf Transmembrane Conductance Regulator

Bronchial mucins from patients suffering from CF (cystic fibrosis) exhibit glycosylation alterations, especially increased amounts of the sialyl-Lewisx (NeuAcα2-3Galβ1-4[Fucα1-3]GlcNAc-R) and 6-sulfo-sialyl-Lewisx (NeuAcα2-3Galβ1-4[Fucα1-3][SO3H-6]GlcNAc-R) terminal structures. These epitopes are preferential receptors for Pseudomonas aeruginosa, the bacteria responsible for the chronicity of airway infection and involved in the morbidity and early death of CF patients. However, these glycosylation changes cannot be directly linked to defects in CFTR (CF transmembrane conductance regulator) gene expression since cells that secrete airway mucins express no or very low amounts of the protein. Several studies have shown that inflammation may affect glycosylation and sulfation of various glycoproteins, including mucins. In the present study, we show that incubation of macroscopically healthy fragments of human bronchial mucosa with IL-6 (interleukin-6) or IL-8 results in a significant increase in the expression of α1,3/4-fucosyltransferases [FUT11 (fucosyltransferase 11 gene) and FUT3], α2-6- and α2,3-sialyltransferases [ST3GAL6 (α2,3-sialyltransferase 6 gene) and ST6GAL2 (α2,6-sialyltransferase 2 gene)] and GlcNAc-6-O-sulfotransferases [CHST4 (carbohydrate sulfotransferase 4 gene) and CHST6] mRNA. In parallel, the amounts of sialyl-Lewisx and 6-sulfo-sialyl-Lewisx epitopes at the periphery of high-molecular-mass proteins, including MUC4, were also increased. In conclusion, our results indicate that IL-6 and -8 may contribute to the increased levels of sialyl-Lewisx and 6-sulfo-sialyl-Lewisx epitopes on human airway mucins from patients with CF.

PRO–CF–MED, Clinical Proof of concept for a RNA–targeting Oligonucleotide for a Cystic fibrosis–F508del MEDication, Horizon2020

Impact ◽  
2018 ◽  
Vol 2018 (3) ◽  
pp. 52-54
Author(s):  
Nicolas Lamontagne
Keyword(s):  
Cystic Fibrosis ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Rna Targeting ◽  
Threatening Condition ◽  
Life Threatening ◽  
Cftr Protein ◽  
Disease Modifying ◽  
Cystic Fibrosis Transmembrane ◽  
Specific Challenge

Cystic fibrosis (CF) is a progressive life–shortening disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene leading to a dysfunctional CFTR protein. The disease affects over 70,000 patients worldwide and while many mutations are known, the F508del mutation affects 90% of all patients. The absence of CFTR in the plasma membrane leads to a dramatic decrease in chloride efflux, resulting in viscous mucus that causes severe symptoms in vital organs like the lungs and intestines. For CF patients that suffer from the life threatening F508del mutation only palliative treatment exist. PRO–CF–MED addresses the specific challenge of this call by introducing the first disease modifying medication for the treatment of the CF patients with F508del mutation. The PRO–CF–MED project has been designed to assess the potential clinical efficacy of QR–010, an innovative disease modifying oligonucleotide–based treatment for F508del patients. Partners within PRO–CF–MED have generated very promising preclinical evidence for QR–010 which allows for further clinical assessment of QR–010 in clinical trials. PRO–CF–MED will enable the fast translation of QR–010 towards clinical practice and market authorisation. PRO–CF–MED has the potential to transform this life–threatening condition into a manageable one.

Cystic fibrosis transmembrane conductance regulator modulators for cystic fibrosis: a new dawn?

2021 ◽  
pp. archdischild-2020-320680
Author(s):  
Claire Edmondson ◽  
Christopher William Course ◽  
Iolo Doull
Keyword(s):  
Cystic Fibrosis ◽  
Life Expectancy ◽  
Respiratory Infections ◽  
Autosomal Recessive Disorder ◽  
Societal Implications ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Potent Effect ◽  
Major Barrier ◽  
Cystic Fibrosis Transmembrane

Cystic fibrosis (CF) is the most common life-limiting inherited condition in Caucasians. It is a multisystem autosomal recessive disorder caused by variants in the gene for cystic fibrosis transmembrane conductance regulator (CFTR) protein, a cell-surface localised chloride channel that regulates absorption and secretion of salt and water across epithelia. Until recently, the treatment for CF was predicated on ameliorating and preventing the downstream symptoms of CFTR dysfunction, primarily recurrent respiratory infections and pancreatic exocrine failure. But a new class of therapy—the CFTR modulators, which treat the basic defect and decrease the complications of CF, leads to significantly improved pulmonary function, decreased respiratory infections and improved nutrition. The newest agent, a combination of elexacaftor, tezacaftor and ivacaftor, will be suitable for approximately 90% of all people with CF and is likely to decrease the morbidity and significantly increase the life expectancy for most people with CF. The major barrier to their widespread introduction has been their cost, with many countries unwilling or unable to fund them. Nevertheless, such is their therapeutic efficacy and their likely potent effect on life expectancy that their advent has wider societal implications for the care of children and adults with CF.

Mutations of Cystic Fibrosis Transmembrane Conductance Regulator Gene Cause a Monocyte-Selective Adhesion Deficiency

2016 ◽  
Vol 193 (10) ◽  
pp. 1123-1133 ◽  
Author(s):  
Claudio Sorio ◽  
Alessio Montresor ◽  
Matteo Bolomini-Vittori ◽  
Sara Caldrer ◽  
Barbara Rossi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Transmembrane Conductance Regulator ◽  
Regulator Gene ◽  
Transmembrane Conductance ◽  
Cystic Fibrosis Transmembrane
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