Article
Multidisciplinary Sciences
Jae Hun Kim, Niccole Schaible, Joseph K. Hall, Erzsebet Bartolak-Suki, Yuqing Deng, Jacob Herrmann, Adam Sonnenberg, Holger P. Behrsing, Kenneth R. Lutchen, Ramaswamy Krishnan, Bela Suki
Summary: By measuring tissue stiffness at both the tissue and alveolar scales, we found that the lung tissue of patients with emphysema was 50% softer due to microscopic septal wall remodeling and structural deterioration. Protein expression profiling revealed a wide range of enzymes involved in septal wall remodeling, along with mechanical forces, leading to rupture and structural deterioration of the emphysematous lung parenchyma.
Article
Multidisciplinary Sciences
Eric Simon, Maciej Motyka, Grietje H. Prins, Mei Li, Werner Rust, Stefan Kauschke, Coralie Viollet, Peter Olinga, Anouk Oldenburger
Summary: There is a need for predictive ex vivo models for NAFLD. This study profiles a new human and mouse PCLSs based assay for steatosis in NAFLD using RNASeq. Steatosis is induced by incremental supplementation of sugars, insulin, and fatty acids, and the gene expression regulation is analyzed across different nutrient conditions and time for both human and mouse liver organ derived PCLSs.
Article
Pathology
Eike B. Preuss, Stephanie Schubert, Christopher Werlein, Helge Stark, Peter Braubach, Anne Hoefer, Edith K. J. Plucinski, Harshit R. Shah, Robert Geffers, Katherina Sewald, Armin Braun, Danny D. Jonigk, Mark P. Kuehnel
Summary: This study provides a comprehensive overview of the histomorphologic and pathologic changes during long-term cultivation of human precision-cut lung slices (PCLS). The results show that while the viability of PCLS is well preserved during long-term cultivation, there is a continuous loss of cells. The integrity of the alveoli is preserved for about 2 weeks, but the vasculatory system experiences significant loss of integrity within the first week. Ciliary beat in the small airways gradually decreases after 1 week, and keratinizing squamous metaplasia of the alveolar epithelium increases over time. Transcriptome analysis reveals an increased immune response and decreased metabolic activity within the first 24 hours after PCLS generation.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Article
Engineering, Biomedical
Haitham Salti, Lea Kramer, Sophie-Charlotte Nelz, Mathias Lorenz, Anne Breitrueck, Jacqueline Hofrichter, Marcus Frank, Karoline Schulz, Steffen Mitzner, Reinhold Wasserkort
Summary: Physical pretreatment with freezing-thawing cycles (FTC) before chemical immersion is the most effective method for decellularization of kidney slices.
BIOMEDICAL MATERIALS
(2023)
Article
Nutrition & Dietetics
Grietje H. Prins, Melany Rios-Morales, Albert Gerding, Dirk-Jan Reijngoud, Peter Olinga, Barbara M. Bakker
Summary: Butyrate has limited impact on the liver in an ex vivo induced MAFLD model, as it does not directly increase lipid beta-oxidation but may help prevent disease progression to NASH and cirrhosis.
Article
Immunology
Nina Cramer, Marie Luise Nawrot, Lion Wege, Marie Dorda, Charline Sommer, Olga Danov, Sabine Wronski, Armin Braun, Danny Jonigk, Sebastian Fischer, Antje Munder, Burkhard Tuemmler
Summary: Chronic respiratory infections with Pseudomonas aeruginosa have a significant impact on the quality of life and prognosis of cystic fibrosis patients. This study investigates the extent to which P. aeruginosa adapts to the CF airways and its influence on the fitness of the pathogen in the lungs. The results suggest that the severity of CF lung disease drives the adaptation of P. aeruginosa more strongly than the bacterial genotype.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Maggie Lam, Emma Lamanna, Louise Organ, Chantal Donovan, Jane E. E. Bourke
Summary: Precision cut lung slices (PCLS) are powerful experimental tools for respiratory research. They have been used to visualize airway and pulmonary artery contractility, assess bronchodilators and vasodilators, and measure disease-related outcomes in various species, including humans. This review highlights the established and innovative uses of PCLS as an intermediary between cellular and organ-based studies, and emphasizes their potential in investigating mechanisms and therapeutic targets for airway contraction and fibrosis in lung diseases.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Toxicology
Roberta Bartucci, Alex Z. van der Meer, Ykelien L. Boersma, Peter Olinga, Anna Salvati
Summary: Testing different nanomaterials on murine liver tissue slices showed that exposure to amino-modified polystyrene nanoparticles in serum-free conditions induced strong inflammation, while no inflammation was observed under serum-supplemented conditions. No clear signs of inflammation or fibrosis were detected after exposure to silica, titania, or carboxylated polystyrene in all tested conditions. These results indicate that tissue responses to nanoparticles can be strongly affected by exposure conditions and the ageing of nanoparticle dispersions.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Engineering, Biomedical
Rachel Blomberg, Kayla Sompel, Caroline Hauer, Alex J. Smith, Brisa Pena, Jennifer Driscoll, Patrick S. Hume, Daniel T. Merrick, Meredith A. Tennis, Chelsea M. Magin
Summary: Lung cancer, the leading cause of cancer-related deaths worldwide, still occurs in people who have quit smoking. Researchers have developed an in vitro model of lung cancer premalignancy using precision-cut lung slices embedded in hydrogel and exposed to a cigarette smoke carcinogen. This model provides a foundation for studying the earliest stages of lung carcinogenesis and potential chemoprevention strategies.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Physiology
Julia Herbert, Jacklyn S. Kelty, Jeffrey D. Laskin, Debra L. Laskin, Andrew J. Gow
Summary: The consumption of e-cigarettes is being regulated due to concerns about toxicity, manufacturing standards, and lung injury. Studies have shown toxicity and oxidative stress caused by e-cigarette aerosols and additives. However, the effects of e-cigarettes on lung tissue are still unclear.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2023)
Article
Medicine, Research & Experimental
Stine Julie Tingskov, Michael Schou Jensen, Casper-Emil Tingskov Pedersen, Isabela Bastos Binotti Abreu de Araujo, Henricus A. M. Mutsaers, Rikke Norregaard
Summary: The study found that the selective estrogen receptor modulator tamoxifen has a mitigating effect on renal fibrosis in female, male, and ovariectomized female rats, as well as demonstrating an anti-fibrotic effect in human kidney slices. Gender differences may play a role in drug treatment response.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Physiology
M. J. R. Ruigrok, M. A. P. Roest, H. W. Frijlink, P. Olinga, W. L. J. Hinrichs, B. N. Melgert
Summary: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally, characterized by impaired epithelial repair. The study shows that RANKL protein contributes to lung repair by reducing cell death.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Anna Gluba-Sagr, Beata Franczyk, Magdalena Rysz-Gorzynska, Janusz Lawinski, Jacek Rysz
Summary: Chronic kidney disease is a significant health concern, with renal fibrosis being a major mechanism of renal dysfunction. MicroRNAs play important roles in the development of fibrosis and chronic kidney disease. However, the effects and regulation of miRNAs may vary in different tissues and cells.
Article
Engineering, Biomedical
Nafiseh Rafiei, Mohammadamir G. Moghadam, Aaron Au, Romario Regeenes, Subbulakshmi Chidambaram, Tao Liang, Yufeng Wang, Christopher M. Yip, Herbert Gaisano, Jonathan Rocheleau
Summary: This article introduces a versatile microfluidic device for 3D fluorescence imaging of mouse or human pancreas PCTs, positioning them within a chamber with tall channels for media exchange. The device localizes shear stress to small regions on tissue surfaces and allows for controlled media exchange at lower flowrates than conventional chambers. It enables high-resolution imaging of immunofluorescently labeled PCTs on a confocal and with a large field of view on a SPIM without compromising image quality.
Article
Medicine, General & Internal
Mitchel J. R. Ruigrok, Khaled E. M. El Amasi, Diana J. Leeming, Jannie M. B. Sand, Henderik W. Frijlink, Wouter L. J. Hinrichs, Peter Olinga
Summary: IPF is a chronic lung disease with an urgent need for more effective drugs, with HSP47 identified as a potential therapeutic target. Targeted siRNA therapy against Serpinh1 showed reduction in fibronectin secretion in fibrotic lung slices, indicating a promising approach for fibrosis treatment.
FRONTIERS IN MEDICINE
(2021)
Article
Cell Biology
Sarannya Edamana, Frederic H. Login, Andreas Riishede, Vibeke S. Dam, Trine Tramm, Lene N. Nejsum
Summary: Breast carcinomas are associated with increased cell proliferation, migration, altered cellular adhesion, and loss of epithelial polarity. Aquaporin-5 (AQP5) is aberrantly expressed in breast cancer and is linked to metastasis and poor prognosis. AQP5 enhances cancer cell proliferation and migration, reduces cell-cell adhesion, and activates the Ras pathway. This study explores the relationship between AQP5 and the polarity protein Scribble. Results show that high AQP5 expression is inversely related to Scribble levels in breast carcinoma tissue samples. Overexpression of AQP5 in breast cancer cells reduces spheroid size, circularity, and Scribble levels. The effect of AQP5 on Scribble is partially dependent on AQP5-mediated activation of Ras. These findings suggest that AQP5 negatively regulates cellular polarity in breast cancer.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Sarannya Edamana, Stine F. Pedersen, Lene N. Nejsum
Summary: Aquaporin (AQP) water channels play a crucial role in the transport of water across cellular membranes and are associated with breast cancer. In vitro studies have shown that AQPs can influence the effectiveness of conventional anticancer chemotherapies. This study focused on AQP1, AQP3, and AQP5, which are often overexpressed in breast cancer, and evaluated their impact on the viability of breast cancer cell spheroids treated with different chemotherapies. The findings support the significant role of AQPs in the response to conventional chemotherapies and highlight the importance of understanding the individual proteins involved in resistance to chemotherapy for personalized medicine in breast cancer.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Immunology
Christina V. Ernstsen, Andreas Riishede, Anne Kristine S. Iversen, Lene Bay, Thomas Bjarnsholt, Lene N. Nejsum
Summary: Chronic wounds are a significant burden on society and are estimated to affect 1-2% of the global population. The expression of E-cadherin and aquaporin-3, important for skin function and cell migration, is found to be low at the edges of chronic wounds according to immunohistochemical stainings. Further studies are needed to understand the association between this downregulation and the pathophysiology of chronic wounds.
Article
Immunology
Soren H. Elsborg, Gitte A. Pedersen, Mia G. Madsen, Anna K. Keller, Rikke Norregaard, Lene N. Nejsum
Summary: Animal and human tissues are commonly used in physiological and pathophysiological research. A new method has been developed to allow for multiplex immunofluorescence staining of kidney sections in order to reuse the same tissue section multiple times, which addresses both ethical concerns and limited availability.
Article
Neurosciences
Maria Venneri, Vanessa Vezzi, Annarita Di Mise, Marianna Ranieri, Mariangela Centrone, Grazia Tamma, Lene N. Nejsum, Giovanna Valenti
Summary: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare X-linked disease caused by gain-of-function mutations of arginine vasopressin receptor 2 (V2R). The constitutive AQP2 trafficking associated with the gain-of-function V2R-R137L/C mutants causing NSIAD is protein kinase A independent and requires an intact Ser269 in AQP2 under the control of ROCK phosphorylation.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Multidisciplinary Sciences
Sren Kissow Lildal, Esben Svs Szocska Hansen, Christoffer Laustsen, Rikke Norregaard, Lotte Bonde Bertelsen, Kirsten Madsen, Camilla W. Rasmussen, Palle Jorn Sloth Osther, Helene Jung
Summary: Intrarenal backflow (IRB) during ureteroscopy is associated with increased intrarenal pressure (IRP) and can occur even at low pressures. This contradicts the common consensus that keeping IRP below 30-35 mmHg eliminates the risk of post-operative infection and sepsis. Therefore, it is important to reduce IRP and operative time during ureteroscopy.
Article
Biology
Henricus A. M. Mutsaers, Michael Schou Jensen, Jean-Claude Kresse, Stine Julie Tingskov, Mia Gebauer Madsen, Rikke Norregaard
Summary: The objective of this study is to establish an animal-free drug screening platform for renal fibrosis using human precision-cut kidney slices (PCKS). The results showed that transforming growth factor-beta (TGF-beta) induced fibrosis in human PCKS and anti-fibrotic compounds altered TGF-beta-induced pro-fibrotic gene expression in human PCKS.
BMC RESEARCH NOTES
(2023)
Article
Biochemistry & Molecular Biology
Antoni Kowalski, Cristine Betzer, Sigrid Thirup Larsen, Emil Gregersen, Estella A. Newcombe, Montana Caballero Bermejo, Viktor Wisniewski Bendtsen, Jorin Diemer, Christina Ernstsen, Shweta Jain, Alicia Espina Bou, Annette Eva Langkilde, Lene N. Nejsum, Edda Klipp, Robert Edwards, Birthe B. Kragelund, Poul Henning Jensen, Poul Nissen
Summary: This study shows that monomeric alpha-synuclein can activate plasma membrane Ca2+-ATPase (PMCA) to promote calcium clearance in neurons. The colocalization of alpha-synuclein and PMCA at neuronal synapses suggests a potential physiological function for alpha-synuclein in regulating calcium expulsion.
Review
Urology & Nephrology
Frederic H. Login, Lene N. Nejsum
Summary: Aquaporins play a crucial role in renal water handling and body water homeostasis. They are also involved in water reabsorption and secretion in other tissues, transport of small molecules and gases, and various cellular processes. Furthermore, the expression of certain AQPs is related to cancer progression and drug response, suggesting their potential application in prognostics and therapeutics.
NATURE REVIEWS NEPHROLOGY
(2023)
Review
Physiology
Rikke Norregaard, Henricus A. M. Mutsaers, Jorgen Frokiaer, Tae-Hwan Kwon
Summary: The kidneys are crucial for maintaining body homeostasis, but ureteral obstruction can negatively affect renal function and lead to renal fibrosis. Experimental unilateral ureteral obstruction (UUO) is a widely used model for studying tubulointerstitial fibrosis, providing valuable insights at the molecular, genomic, and cellular levels. However, this model has limitations in studying tubular injury and repair as well as its translation to humans.
PHYSIOLOGICAL REVIEWS
(2023)
Article
Cell Biology
Pernille Bogetofte Thomasen, Alena Salasova, Kasper Kjaer-Sorensen, Lucie Woloszczukova, Josef Lavicky, Hande Login, Jeppe Tranberg-Jensen, Sergio Almeida, Sander Beel, Michaela Kavkova, Per Qvist, Mads Kjolby, Peter Lund Ovesen, Stella Nolte, Benedicte Vestergaard, Andreea-Cornelia Udrea, Lene Niemann Nejsum, Moses Chao, Philip Van Damme, Jan Krivanek, Jeremy Dasen, Claus Oxvig, Anders Nykjaer
Summary: SorCS2 is a receptor for PGRN that plays an important role in MN diversification and axon outgrowth, as well as affecting neuromuscular junction morphology and fish motility. Deficiency of SorCS2 disrupts cell-fate decisions of brachial MNs and leads to innervation deficits of posterior nerves. In addition, SorCS2 knockout mice exhibit slower motor nerve regeneration. The interaction between primitive macrophages expressing high levels of PGRN and SorCS2-positive motor axons is crucial for axon pathfinding.
Article
Physiology
Jacob Rudjord Therkildsen, Stine Julie Tingskov, Michael Schou Jensen, Helle Praetorius, Rikke Norregaard
Summary: P2X(7) receptor plays a regulatory role in late-stage fibrosis by reducing neutrophil-dependent interstitial MMP8 release, resulting in less macrophage infiltration and reduced matrix accumulation.
PHYSIOLOGICAL REPORTS
(2023)
Letter
Medicine, Research & Experimental
Henricus A. M. Mutsaers, Camilla Merrild, Rikke Norregaard, Oleguer Plana-Ripoll
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Review
Physiology
Minyu Zhang, Biyang Xiao, Xiaoqi Chen, Bingming Ou, Songtao Wang
Summary: Non-alcoholic fatty liver disease (NAFLD) is closely related to bile acid and gut microbiota disorders. Exercise plays an important role in maintaining the homeostasis of the enterohepatic circulation and the health of the host gut microbiota by regulating the composition and function of the bile acid pool in the enterohepatic axis. Exercise has been recommended as a first-line intervention for NAFLD, and regulating bile acids through exercise may be a promising treatment strategy.
