Special Issue "The Tight Junction and Its Proteins: From Structure to Pathologies".

Most tight junction (TJ) proteins build epithelial and endothelial barriers [...

TAM receptors mediate the Fpr2-driven pain resolution and fibrinolysis after nerve injury.

Nerve injury causes neuropathic pain and multilevel nerve barrier disruption. Nerve barriers consist of perineurial, endothelial and myelin barriers. So far, it is unclear whether resealing nerve barriers fosters pain resolution and recovery.

Molecular and Functional Characterization of the Peritoneal Mesothelium, a Barrier for Solute Transport.

Peritoneal dialysis (PD) is an increasingly needed, life-maintaining kidney replacement therapy; efficient solute transport is critical for patient outcome. While the role of peritoneal perfusion on solute transport in PD has been described, the role of cellular barriers is uncertain, the mesothelium has been considered irrelevant. We calculated peritoneal blood microvascular endothelial (BESA) to mesothelial surface area (MSA) ratio in human peritonea in health, chronic kidney disease, and on PD, and performed molecular transport related gene profiling and single molecule localization microscopy in two mesothelial (MC) and two endothelial cell lines (EC).

Wall of Resilience: How the Intestinal Epithelium Prevents Inflammatory Onslaught in the Gut.

The intestinal epithelium forms the boundary between the intestinal immune system in the lamina propria and the outside world, the intestinal lumen, which contains a diverse array of microbial and environmental antigens. Composed of specialized cells, this epithelial monolayer has an exceptional turnover rate. Differentiated epithelial cells are released into the intestinal lumen within a few days, at the villus tip, a process that requires strict regulation.

Expression and Localization Profiles of Tight Junction Proteins in Immune Cells Depend on Their Activation Status.

The ability of the immune system to combat pathogens relies on processes like antigen sampling by dendritic cells and macrophages migrating through endo- and epithelia or penetrating them with their dendrites. In addition, other immune cell subtypes also migrate through the epithelium after activation. For paracellular migration, interactions with tight junctions (TJs) are necessary, and previous studies reported TJ protein expression in several immune cells.

Knock-out of dipeptidase CN2 in human proximal tubular cells disrupts dipeptide and amino acid homeostasis and para- and transcellular solute transport.

Aim: Although of potential biomedical relevance, dipeptide metabolism has hardly been studied. We found the dipeptidase carnosinase-2 (CN2) to be abundant in human proximal tubules, which regulate water and solute homeostasis. We therefore hypothesized, that CN2 has a key metabolic role, impacting proximal tubular transport function.

A Colonic Organoid Model Challenged with the Large Toxins of TcdA and TcdB Exhibit Deregulated Tight Junction Proteins.

Background: toxins TcdA and TcdB are responsible for diarrhea and colitis. Lack of functional studies in organoid models of the gut prompted us to elucidate the toxin's effects on epithelial barrier function and the molecular mechanisms for diarrhea and inflammation.

Methods: Human adult colon organoids were cultured on membrane inserts.

Solving the Puzzle: Molecular Research in Inflammatory Bowel Diseases.

Inflammatory bowel disease (IBD) encompasses chronic idiopathic relapsing and remitting gastrointestinal autoimmune diseases characterized by chronic inflammatory disorders of complex etiology, posing clinical challenges due to their often therapy-refractory nature [...

Myelin barrier breakdown, mechanical hypersensitivity, and painfulness in polyneuropathy with claudin-12 deficiency.

Background: The blood-nerve and myelin barrier shield peripheral neurons and their axons. These barriers are sealed by tight junction proteins, which control the passage of potentially noxious molecules including proinflammatory cytokines via paracellular pathways. Peripheral nerve barrier breakdown occurs in various neuropathies, such as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and traumatic neuropathy.

Macromolecule Translocation across the Intestinal Mucosa of HIV-Infected Patients by Transcytosis and through Apoptotic Leaks.

Based on indirect evidence, increased mucosal translocation of gut-derived microbial macromolecules has been proposed as an important pathomechanism in HIV infection. Here, we quantified macromolecule translocation across intestinal mucosa from treatment-naive HIV-infected patients, HIV-infected patients treated by combination antiretroviral therapy, and HIV-negative controls and analyzed the translocation pathways involved. Macromolecule permeability was quantified by FITC-Dextran 4000 (FD4) and horseradish peroxidase (HRP) flux measurements.

Physical activity promotion in daycare centres in Germany: study protocol for a cross-sectional survey within the BeweKi study.

Introduction: In Germany, a total of 92.2% of children between the age of 3 and school entry age attend daycare centres. Therefore, daycare centres are a suitable setting to promote physical activity among children.

Proteolytic Activity of the Paracaspase MALT1 Is Involved in Epithelial Restitution and Mucosal Healing.

The paracaspase MALT1 is a crucial regulator of immune responses in various cellular contexts. Recently, there is increasing evidence suggesting that MALT1 might represent a novel key player in mucosal inflammation. However, the molecular mechanisms underlying this process and the targeted cell population remain unclear.

Oncogenic signaling is coupled to colorectal cancer cell differentiation state.

Colorectal cancer progression is intrinsically linked to stepwise deregulation of the intestinal differentiation trajectory. In this process, sequential mutations of APC, KRAS, TP53, and SMAD4 enable oncogenic signaling and establish the hallmarks of cancer. Here, we use mass cytometry of isogenic human colon organoids and patient-derived cancer organoids to capture oncogenic signaling, cell phenotypes, and differentiation states in a high-dimensional single-cell map.

Change in sports activity and walking and cycling for transport since the COVID-19 pandemic - Results of the GEDA 2021 study.

Background: Physical activity is a significant health promotion behaviour. COVID-19 pandemic mitigation measures, such as reducing social contact, closing sports facilities and working from home offices, may make it more difficult to engage in regular physical activity.

Methods: The data collected between July and October 2021 from the nationally representative study German Health Update (GEDA 2021) were used.

ZO-1 Guides Tight Junction Assembly and Epithelial Morphogenesis via Cytoskeletal Tension-Dependent and -Independent Functions.

Formation and maintenance of tissue barriers require the coordination of cell mechanics and cell-cell junction assembly. Here, we combined methods to modulate ECM stiffness and to measure mechanical forces on adhesion complexes to investigate how tight junctions regulate cell mechanics and epithelial morphogenesis. We found that depletion of the tight junction adaptor ZO-1 disrupted junction assembly and morphogenesis in an ECM stiffness-dependent manner and led to a stiffness-dependant reorganisation of active myosin.

How much do adults sit? Results from the German Health Update (GEDA 2019/2020-EHIS).

Background: Sedentary behaviour is increasingly perceived as a risk factor for the development of diseases and for increased mortality. In particular, increased time spent sitting in combination with low physical activity seems to have negative health consequences.

Methods: In the nationwide cross-sectional study German Health Update (GEDA 2019/2020-EHIS), the indicator 'sitting' was captured by the self-report of the participants.

MicroRNA-21-5p functions via RECK/MMP9 as a proalgesic regulator of the blood nerve barrier in nerve injury.

Both nerve injury and complex regional pain syndrome (CRPS) can result in chronic pain. In traumatic neuropathy, the blood nerve barrier (BNB) shielding the nerve is impaired-partly due to dysregulated microRNAs (miRNAs). Upregulation of microRNA-21-5p (miR-21) has previously been documented in neuropathic pain, predominantly due to its proinflammatory features.

Human duodenal organoid-derived monolayers serve as a suitable barrier model for duodenal tissue.

Usually, duodenal barriers are investigated using intestinal cell lines like Caco-2, which in contrast to native tissue are limited in cell-type representation. Organoids can consist of all intestinal cell types and are supposed to better reflect the in vivo situation. Growing three-dimensionally, with the apical side facing the lumen, application of typical physiological techniques to analyze the barrier is difficult.

Tight junction channels claudin-10b and claudin-15: Functional mapping of pore-lining residues.

Although functional and structural models for paracellular channels formed by claudins have been reported, mechanisms regulating charge and size selectivity of these channels are unknown in detail. Here, claudin-15 and claudin-10b cation channels showing high-sequence similarity but differing channel properties were analyzed. Mutants of pore-lining residues were expressed in MDCK-C7 cells.

MarvelD3 Is Upregulated in Ulcerative Colitis and Has Attenuating Effects during Colitis Indirectly Stabilizing the Intestinal Barrier.

In inflammatory bowel disease (IBD), the impaired intestinal barrier is mainly characterized by changes in tight junction protein expression. The functional role of the tight junction-associated MARVEL protein MARVELD3 (MD3) in IBD is yet unknown. (i) In colon biopsies from IBD patients we analyzed MD3 expression and (ii) in human colon HT-29/B6 cells we studied the signaling pathways of different IBD-relevant cytokines.

Health-promoting behaviour among adults in Germany - Results from GEDA 2019/2020-EHIS.

Health-promoting behaviours are important at any age to prevent diseases and to promote well-being. Using data from GEDA 2019/2020-EHIS, a Germany-wide, representative survey, this article describes how often the adult population in Germany reports certain types of health-promoting behaviour in their everyday lives. The behaviours considered are nonsmoking, low-risk alcohol consumption, achievement of the World Health Organization's (WHO) recommendations on aerobic physical activity, at least daily fruit and vegetable consumption, and maintaining a body weight within the normal range.

From 3D to 2D: Harmonization of Protocols for Two-dimensional Cultures on Cell Culture Inserts of Intestinal Organoids from Various Species.

In the expanding field of intestinal organoid research, various protocols for three- and two-dimensional organoid-derived cell cultures exist. Two-dimensional organoid-derived monolayers are used to overcome some limitations of three-dimensional organoid cultures. They are increasingly used also in infection research, to study physiological processes and tissue barrier functions, where easy experimental access of pathogens to the luminal and/or basolateral cell surface is required.

Exercise and Carotid Properties in the Young-The KiGGS-2 Study.

Carotid intima-media thickness (cIMT) and stiffness (cS) are predictive markers of early vascular aging and atherosclerotic risk. This study assessed, whether exercise has protective effects on carotid structure and function or on vascular risk in the young. Volume and change of exercise (recreational and organized sports participation) of German adolescents and young adults was assessed within the prospective population-study KiGGS at KiGGS-Wave-1 (2009-2012) and KiGGS-Wave-2 (2014-2017) using standardized self-reporting questionnaires.

Claudin-10a Deficiency Shifts Proximal Tubular Cl Permeability to Cation Selectivity Claudin-2 Redistribution.

Background: The tight junction proteins claudin-2 and claudin-10a form paracellular cation and anion channels, respectively, and are expressed in the proximal tubule. However, the physiologic role of claudin-10a in the kidney has been unclear.

Methods: To investigate the physiologic role of claudin-10a, we generated claudin-10a-deficient mice, confirmed successful knockout by Southern blot, Western blot, and immunofluorescence staining, and analyzed urine and serum of knockout and wild-type animals.