Article
Biochemistry & Molecular Biology
Aida Zulueta, Michele Dei Cas, Francesco Luciano, Alessandra Mingione, Francesca Pivari, Ilaria Righi, Letizia Morlacchi, Lorenzo Rosso, Paola Signorelli, Riccardo Ghidoni, Rita Paroni, Anna Caretti
Summary: The role of S1P in Cystic Fibrosis has been studied since 2001, with research showing that CFTR mutation in CF patients is associated with altered S1P expression. CF patients show increased S1P accumulation due to up-regulation of SphK1 and down-regulation of SGPL1, along with deficient expression of Spns2 transporter. This excessive accumulation is partially prevented by up-regulated phosphatases in CF cells.
Article
Cell Biology
Onofrio Laselva, Caterina Allegretta, Sante Di Gioia, Carlo Avolio, Massimo Conese
Summary: DMF demonstrates anti-inflammatory and antioxidant effects in CF treatment, reducing inflammatory responses, restoring CFTR function, and potentially serving as a novel drug to ameliorate lung inflammation in CF patients and enhance drug efficacy.
Article
Microbiology
Shekooh Behroozian, Inmaculada Sampedro, Basanta Dhodary, Stephanie Her, Qianru Yu, Bruce A. Stanton, Jane E. Hill
Summary: Cystic fibrosis is a life-threatening multi-organ disease characterized by susceptibility to chronic pulmonary infections. Bile is believed to contribute to the colonization and pathogenesis of Pseudomonas aeruginosa in the lung.
Article
Immunology
Beate Illek, Horst Fischer, Terry E. Machen, Gopika Hari, Karl V. Clemons, Gabriele Sass, Jose A. G. Ferreira, David A. Stevens
Summary: This study established a fungal epithelial co-culture model to investigate the impact of Aspergillus fumigatus (Af) infection on cystic fibrosis (CF) bronchial epithelial barrier function. The results showed that Af infection resulted in bronchial epithelial cell damage and impaired epithelial barrier function, which was exacerbated in the absence of CFTR. The study also found that Gliotoxin, a major virulence factor of Af, rapidly disrupted the epithelial barrier function and induced chloride secretion in the presence of CFTR.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Microbiology
Katie Dunne, Emma Reece, Siobhan McClean, Sean Doyle, Thomas R. Rogers, Philip Murphy, Julie Renwick
Summary: Aspergillus fumigatus, the most commonly isolated fungus in chronic lung diseases, can disrupt tight junction integrity of human bronchial epithelial cells and cause airway damage.
Article
Pharmacology & Pharmacy
Zsolt Bene, Zsolt Fejes, Tibor Gabor Szanto, Ferenc Fenyvesi, Judit Varadi, Luka A. Clarke, Gyorgy Panyi, Milan Macek, Margarida D. Amaral, Istvan Balogh, Bela Nagy
Summary: In this study, it was found that decreased HE4 protein levels in CF patients treated with CFTR potentiator therapy were inversely correlated with lung function improvement. Modulation of CFTR function affected HE4 expression in CFBE cells, with activation of NF-kappa B pathway playing a role in regulating HE4 expression.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Sara Van den Bossche, Lisa Ostyn, Valerie Vandendriessche, Charlotte Rigauts, Herlinde De Keersmaecker, Cheryl A. Nickerson, Aurelie Crabbe
Summary: In vitro models of differentiated respiratory epithelium are crucial for exploring new therapeutics for chronic respiratory diseases. This study developed three-dimensional models of bronchial epithelial cell lines that closely resemble the in vivo tissue. The models were compared to traditional two-dimensional cultures and air-liquid interface cultures, and showed promising potential as an alternative for in vivo studies.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Nutrition & Dietetics
Rosara Milstein Bass, Alyssa Tindall, Saba Sheikh
Summary: This study examined the diet quality of young adults with CF and found it to be poor compared to the general population. Given the increasing prevalence of overweight and obesity in CF, updated dietary guidance is urgently needed.
Article
Immunology
Yanina Andrea Lamberti, Martina Debandi, Mariela del Carmen Carrica, Jimena Alvarez Hayes, Maria Eugenia Rodriguez
Summary: Inquilinus limosus can survive and replicate inside bronchial epithelial cells, displaying pathogenic properties of antibiotic resistance and chronic infection.
MICROBIAL PATHOGENESIS
(2022)
Article
Multidisciplinary Sciences
Parameet Kumar, Dharmendra Kumar Soni, Chaitali Sen, Mads B. Larsen, Krystyna Mazan-Mamczarz, Yulan Piao, Supriyo De, Myriam Gorospe, Raymond A. Frizzell, Roopa Biswas
Summary: SFPQ expression is reduced in CF lung epithelial cells, but overexpression can increase F508del-CFTR expression and rescue function by modulating cellular signaling pathways. This study is the first to report on the role of SFPQ in regulating the expression and function of F508del-CFTR in CF lung disease, providing insights into potential epigenetic therapeutic targets.
SCIENTIFIC REPORTS
(2021)
Letter
Respiratory System
Aravind A. Menon, Minyi Lee, Xu Ke, Rachel K. Putman, Takuya Hino, Jonathan A. Rose, Fenghai Duan, Samuel Y. Ash, Michael H. Cho, George T. O'Connor, Josee Dupuis, Hiroto Hatabu, Marc E. Lenburg, Ehab S. Billatos, Gary M. Hunninghake, DECAMP Investigators
Summary: This study found that abnormal inflammatory processes are apparent in the bronchial airway gene expression profiles of smokers with and without lung cancer with ILA, suggesting the presence of inflammation in ILA patients and providing new clues for early detection and treatment of disease progression.
RESPIRATORY RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Duncan E. Keegan, John J. Brewington
Summary: The emergence of highly effective CFTR modulator therapy has significantly improved healthcare for most cystic fibrosis (CF) patients. However, accessibility remains a challenge for some due to rare CFTR variants or lack of biologic activity of available therapies. The use of primary human cell-based models, particularly nasal cells, is proposed as a solution to address this gap and is crucial for personalized patient care in CF research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Respiratory System
Martha Dohna, Hilmar Kuehl, Sivagurunathan Sutharsan, Christian Dohna-Schwake, Van Dai Vo Chieu, Susanne Hellms, Norman Kornemann, Diane M. Renz, Michael J. Montag
Summary: Bronchial arteries with a diameter of ≥3.5 mm and the presence of hypertrophied non-bronchial systemic arteries are correlated with massive hemoptysis in CF patients and may serve as predictors for the risk of massive hemoptysis.
BMC PULMONARY MEDICINE
(2022)
Article
Pediatrics
Ralph Fingerhut, Corina Rueegg, Orell Imahorn, Eva Sophie Lunde Pedersen, Claudia Kuehni, Sabina Gallati, Nicolas Regamey, Jurg Barben
Summary: This study describes the newborn screening (NBS) results for cystic fibrosis (CF) in Switzerland since 2011 and highlights the importance of gestational age and day of sampling in interpreting the results. Furthermore, it emphasizes the significance of a second immuno-reactive trypsinogen (IRT) measurement for inconclusive diagnoses.
ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION
(2023)
Article
Respiratory System
Anne Bertelsen, J. Stuart Elborn, Bettina C. Schock
Summary: The study indicates a relationship between P. aeruginosa and anaerobic Prevotella spp., showing that P. histicola and P. nigresens can reduce the growth of P. aeruginosa and dampen the inflammatory response in airway epithelial cells. These findings suggest potential therapeutic approaches to combat chronic P. aeruginosa infection in people with CF.
JOURNAL OF CYSTIC FIBROSIS
(2021)
Article
Biochemistry & Molecular Biology
Aaron G. Liebsch, Hermann Schillers
Summary: The study demonstrated that the anticoagulant heparin can inhibit the interaction between cancer cells and platelets, reducing the formation of the platelet cloak and ultimately decreasing metastasis rates and improving survival. The research also quantified the efficacy of heparin in blocking platelet adhesion to cancer cells and identified P-selectin as a key target for heparin's antimetastatic effect.
JOURNAL OF MOLECULAR RECOGNITION
(2021)
Article
Urology & Nephrology
Ali S. Alzahrani, Maged Hussein, Meshael Alswailem, Ahmad Mouna, Lina Albalawi, Yosra Moria, Mai Abdel Jabbar, Yufei Shi, Dorothee Guenzel, Majed Dasouki
Summary: A novel CLDN10 mutation was identified in two unrelated Saudi families with HELIX syndrome, disrupting the C-terminus pdz-binding motif of claudin-10. Functional studies indicated that this mutation led to mRNA degradation, protein retention in intracellular compartments, and translocation of other claudins in renal and sweat gland tissues.
KIDNEY INTERNATIONAL
(2021)
Article
Allergy
Roman Mannweiler, Sophia Bergmann, Sabine Vidal-y-Sy, Johanna M. Brandner, Dorothee Guenzel
Summary: This study utilized impedance spectroscopy to separate the barrier properties of the stratum corneum (SC) and viable epidermis (VE), and evaluate the impact of Cldn1 and 4 knockdown on the skin barrier. The results showed that the resistance drop induced by Cldn1 knockdown arises from impairment of both SC and VE, and non-invasive detection of Cldn1 knockdown was achieved through time-dependent frequency shifts with hyperosmolar electrolyte penetration.
Article
Urology & Nephrology
Tilman Breiderhoff, Nina Himmerkus, Luca Meoli, Anja Fromm, Sebastian Sewerin, Natalia Kriuchkova, Oliver Nagel, Yury Ladilov, Susanne M. Krug, Catarina Quintanova, Meike Stumpp, Dieter Garbe-Schoenberg, Ulrike Westernstroeer, Cosima Merkel, Merle Annette Brinkhus, Janine Altmuller, Michal R. Schweiger, Dominik Muller, Kerim Mutig, Markus Morawski, Jan Halbritter, Susanne Milatz, Markus Bleich, Dorothee Guenzel
Summary: Recent study indicates that claudin-10a is the major paracellular anion channel in the proximal tubule, and its deficiency leads to excessive reabsorption of calcium and magnesium. Various analyses, including electrophysiological studies, suggest compensatory transcellular transport in proximal and distal tubule segments, as well as metabolic adaptation in the proximal tubule, to counterbalance the loss of paracellular anion permeability.
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Hematology
Nadine Martins Castanheira, Anna K. Spanhofer, Sebastian Wiener, Stefanie Bobe, Hermann Schillers
Summary: The study revealed that cancer cells hijack platelets by phagocytosis and recycling of platelet membrane proteins, aiding in cancer cell survival and metastasis. The process of platelet uptake can be tracked, with positive platelet uptake observed in tested cancer cells but not in non-cancerous cells.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Multidisciplinary Sciences
Caroline Hempel, Rita Rosenthal, Anja Fromm, Susanne M. Krug, Michael Fromm, Dorothee Gunzel, Joerg Piontek
Summary: This study analyzed the structural and functional differences between claudin-15 and claudin-10b cation channels and identified several mutants that affect ion permeability and pore diameter. Furthermore, the study revealed that the charge at the W63/K64 position has an impact on the assembly and properties of claudin-10b channels but not claudin-15 channels.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Article
Immunology
Yiyu Wang, Joerg Scheffel, Carolina Ayala Vera, Wei Liu, Dorothee Guenzel, Dorothea Terhorst-Molawi, Marcus Maurer, Sabine Altrichter
Summary: This study aimed to assess the rate and extent of impaired sweating in patients with cholinergic urticaria (CholU) and its association with disease duration and severity. The results showed that reduced sweating is common in CholU patients, especially in those with long-standing and severe disease. The reduced expression of CHRM3 and ACh-E may be responsible for the impaired sweating in these patients.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Laura-Sophie Beier, Ayk Waldow, Saeed Khomeijani Farahani, Roman Mannweiler, Sabine Vidal-Y-Sy, Johanna M. Brandner, Jorg Piontek, Dorothee Gunzel
Summary: The formation of tight junction (TJ) is crucial for epidermal barrier function. Manipulation of TJ barriers in reconstructed human epidermis (RHE) was achieved through knockdown of claudin-1 and -4 or by using claudin-binding fusion proteins. The study demonstrates the critical role of claudin-1 in regulating paracellular permeability in the viable epidermis.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Article
Multidisciplinary Sciences
Catarina Quintanova, Nina Himmerkus, Samuel L. Svendsen, Otto von Schwerdtner, Cosima Merkel, Lennart Pinckert, Kerim Mutig, Tilman Breiderhoff, Dominik Mueller, Dorothee Guenzel, Markus Bleich
Summary: Claudin-10b is an important component of the tight junction and allows paracellular sodium transport in the thick ascending limb of Henle's loop. It colocalizes with the basolateral Na+-K+ ATPase and the Cl- channel subunit barttin, and its absence increases the accessibility of the basolateral extracellular space to certain substances. Electron microscopy reveals a widening of basolateral membrane infoldings in the absence of Claudin-10b. These findings suggest that Claudin-10b may shape neighboring membrane invaginations through trans interaction, thereby stabilizing and facilitating high-flux salt transport.
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES
(2022)
Article
Multidisciplinary Sciences
Hannes Gonschior, Christopher Schmied, Rozemarijn Eva Van der Veen, Jenny Eichhorst, Nina Himmerkus, Joerg Piontek, Dorothee Guenzel, Markus Bleich, Mikio Furuse, Volker Haucke, Martin Lehmann
Summary: Through super-resolution microscopy and fluorescence resonance energy transfer, this study reveals the nanoscale organization principles of tight junctions formed by different claudins. The segregation of channel-forming and barrier-forming claudins allows tight junctions to maintain their barrier function while enabling specific paracellular ion flux.
NATURE COMMUNICATIONS
(2022)
Article
Physiology
Natalia Kriuchkova, Tilman Breiderhoff, Dominik Mueller, Duygu Elif Yilmaz, Hasan Demirci, Hoora Drewell, Dorothee Guenzel, Nina Himmerkus, Markus Bleich, Pontus B. Persson, Kerim Mutig
Summary: Perturbed calcium homeostasis in familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) limits life expectancy. FHHNC is caused by loss-of-function mutations in CLDN16 or CLDN19 genes, leading to impaired paracellular reabsorption of divalent cations in the cortical thick ascending limb (cTAL). Furosemide, a loop diuretic, can compensate for this impairment by activating Ca2+ transport proteins in the distal nephron and collecting duct, resulting in reduced hypercalciuria.
Article
Physiology
Dorothee Guenzel
Summary: The concept of solvent drag involves the frictional coupling between water and solutes in the same pore for transport. It has been applied to transport processes across cell membranes and along the paracellular pathway. Water-driven solute transport has been proposed as the major mechanism for absorption in the small intestine and reabsorption in the renal proximal tubule. However, the discovery of aquaporins and the claudin protein family has led to a reassessment of the solvent drag concept for transepithelial water and solute transport.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)
Review
Urology & Nephrology
Luca Meoli, Dorothee Guenzel
Summary: Sequential expression of claudins in the nephron mirrors the sequential expression of ion channels and transporters, contributing to the maintenance of electrolyte and water homeostasis. The regulation and dysregulation of claudins have been extensively studied in the gastrointestinal tract, but their role in the kidney is only just emerging. Investigating the role of claudins in kidney diseases may provide insights into potential prognostic markers or druggable targets.
NATURE REVIEWS NEPHROLOGY
(2023)
Article
Multidisciplinary Sciences
Matthias Wuttke, Eva Koenig, Maria-Alexandra Katsara, Holger Kirsten, Saeed Khomeijani Farahani, Alexander Teumer, Yong Li, Martin Lang, Burulca Goecmen, Cristian Pattaro, Dorothee Guenzel, Anna Koettgen, Christian Fuchsberger
Summary: A genotype imputation approach was applied to whole exome sequencing data from the UK Biobank, resulting in the discovery of 158 rare variants and 105 genes significantly associated with kidney function traits. This approach boosts statistical power and provides a comprehensive resource for directing experimental and clinical studies of kidney disease.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Sebastian Sewerin, Jorg Piontek, Ria Schonauer, Sonja Grunewald, Angelika Rauch, Steffen Neuber, Carsten Bergmann, Dorothee Gunzel, Jan Halbritter
Summary: This study investigated the molecular basis and phenotypic consequences of a CLDN10 gene variant, which disrupts the assembly of tight junction (TJ) strands. The mutant proteins compromised the function of TJ and exhibited tissue-specific insertion into TJs.
