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Genetics at the Cell Level
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
Valentina Lorenzi, Roser Vento-Tormo
Notably, in 2018, transcriptomic profiling of human bronchial epithelial cells with single-cell sequencing technologies led to the identification of a rare lung cell type that plays a major role in cystic fibrosis (Plasschaert et al., 2018). Named the pulmonary ionocyte, this cell type expresses high levels of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which codes for a cell membrane protein that allows the outward flow of chloride ions and which is mutated in patients with cystic fibrosis, causing pathogenic accumulation of mucus in the airways. Currently available drugs for treating cystic fibrosis are able to target specific mutated versions of the CFTR protein, and knowing which cells are contributing to the production of the protein could be conducive to more precise delivery of the treatment.
Oxidative Stress and Exercise Tolerance in Cystic Fibrosis
Published in James N. Cobley, Gareth W. Davison, Oxidative Eustress in Exercise Physiology, 2022
Cassandra C. Derella, Adeola A. Sanni, Ryan A. Harris
Cystic fibrosis (CF) is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which alters the regulation of chloride entering and leaving the cells (Radlovic, 2012). The CFTR gene mutation alters the production, expression, and activity of the CFTR chloride channel and although millions of people are carriers of the CFTR mutation (National Heart, 2018), only ~35,000 people in the United States (Centers for Disease Control and Prevention, 2020) and ~100,000 people worldwide currently have overt CF. Cystic fibrosis was once regarded as a lung disease due to the pulmonary manifestations and the fact that lung infections are the primary cause of morbidity and mortality. However, given that CFTR is also ubiquitously expressed throughout the body in organs such as the intestines, kidneys, pancreases, and liver, CF is now recognized as a multisystemic condition that requires a multidisciplinary approach to the presenting CF-related diabetes, pancreatic insufficiency, and GI malabsorption (Xue et al., 2016). In addition, CFTR is expressed on other cell types including endothelial cells, skeletal muscle, macrophages, lymphocytes, and mast cells (Xue et al., 2016).
Chronic Liver Disease
Published in Praveen S. Goday, Cassandra L. S. Walia, Pediatric Nutrition for Dietitians, 2022
Julia M. Boster, Kelly A. Klaczkiewicz, Shikha S. Sundaram
Cystic fibrosis (CF) is a genetic disorder caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) (Chapter 19). Dysfunction in this enzyme leads to abnormally thick secretions in the lungs (resulting in chronic pulmonary infections and injury), pancreas (resulting in pancreatic insufficiency), and bile ducts. There are varied hepatobiliary manifestations of CF, including neonatal cholestasis, gallbladder disease, mild transaminase elevation, steatosis, and very rarely, cirrhosis. While management of CF has historically been supportive, emerging therapies such as highly effective CFTR modulators are changing the overall outcomes of children with CF. The impact of these new therapies on liver disease is currently unknown. See Chapter 19 for more information on CF.
Cystic Fibrosis Transmembrane Conductance Regulator Attenuates Oxidative Stress-Induced Injury in Diabetic Retinopathy Rats
Published in Current Eye Research, 2023
Hui Wang, Xian Su, Qian-Qian Zhang, Ying-Ying Zhang, Zhan-Ya Chu, Zhao-Hui Sun, Jin-Ling Zhang, Yu-Fen Tang
Cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic adenosine monophosphate (cAMP) activator, a member of the ATP-binding cassette (ABC) transporter family, and an ATP-dependent chloride channel.8 CFTR has been found to be expressed in many tissues and organs, which could regulate cell apoptosis triggered by oxidative stress via the mitochondrial mechanism.9 Ya-Ping Zhang et al. reported that over-expressed CFTR can inhibit the mitochondrial oxidative stress to protect cerebral tissues from cell apoptosis induced by ischemia-reperfusion injury.10 Besides, gene mutations of CFTR can cause cystic fibrosis (CF)-related diseases, and CFTR defects in pancreatic ducts can directly lead to cystic fibrosis-related diabetes (CFRD).11 In the study by Holly Gaines et al. CFTR was found to play an effective therapeutic role in patients with CFRD.12 Yet, it is still unclear if CFTR can play a regulatory role in DR and there is no relevant report. Interestingly, Yang Fei et al. have demonstrated that CFTR can inhibit NF-κB and MAPK signaling pathways to alleviate high glucose-induced oxidative stress and inflammation in endothelial cells, which indicated that CFRT may be a novel strategy in preventing endothelial dysfunction in diabetes.13 Therefore, we speculated that CFTR can regulate oxidative stress-induced injury in DR.
Epithelial damage in the cystic fibrosis lung: the role of host and microbial factors
Published in Expert Review of Respiratory Medicine, 2022
Arlene M. A. Glasgow, Catherine M. Greene
Cystic fibrosis (CF) is a genetic disease caused by loss of function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Loss of functional CFTR affects several organs including the intestine, pancreas, and liver, however the manifestations in the lung are the most harmful and are responsible for the majority of morbidity and mortality in people with CF. CF lung disease is characterized by tissue damage, airway surface liquid (ASL) layer dehydration, mucus obstruction, bacterial colonization, and chronic inflammation. Collectively, these lead to airflow obstruction, recurrent infective exacerbations, and progressive decline in lung function. Many of these characteristics are also relevant to the chronic obstructive pulmonary disease (COPD) lung which shares various pathophysiological aspects with CF, especially with respect to the pulmonary epithelium [1].
Adherence to cystic fibrosis transmembrane conductance regulator (CFTR) modulators: analysis of a national specialty pharmacy database
Published in Journal of Drug Assessment, 2021
Zumi Mehta, Khalid M. Kamal, Richard Miller, Jordan R. Covvey, Vincent Giannetti
Cystic fibrosis (CF) is a progressive, autosomal recessive genetic disorder. It manifests in multiple organs and systems including the respiratory, digestive, and reproductive system1. For most patients, morbidity and premature mortality are associated with chronic airway infection, progressive loss of lung function, and development of potentially fatal lung disease2. Some other complications associated with CF include pancreatic insufficiency, intestinal malabsorption, diabetes, and pain or discomfort3. The primary cause of CF is mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This gene encodes the CFTR protein, which is mainly responsible for regulating sodium and chloride transport across epithelial cell membranes. The absence or inadequate functioning of CFTR protein results in thick mucus buildup leading to blockage of airways, respiratory difficulties, and subsequently affecting multiple systems and organs4. More than 2000 CFTR gene variants have been identified so far and over 350 mutations have been classified as disease causing, with F508del being the most predominant mutation seen in over 70% of CF cases5–7.