Breaking the Gingival Barrier in Periodontitis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(5), P. 4544 - 4544

Published: Feb. 25, 2023

The break of the epithelial barrier gingiva has been a subject minor interest, albeit playing key role in periodontal pathology, transitory bacteraemia, and subsequent systemic low-grade inflammation (LGI). significance mechanically induced bacterial translocation (e.g., via mastication teeth brushing) disregarded despite accumulated knowledge mechanical force effects on tight junctions (TJs) pathology other tissues. Transitory bacteraemia is observed as rule gingival inflammation, but rarely clinically healthy gingiva. This implies that TJs inflamed deteriorate, e.g., surplus lipopolysaccharide (LPS), proteases, toxins, Oncostatin M (OSM), neutrophil proteases. inflammation-deteriorated rupture when exposed to physiological forces. characterised by during briefly after brushing, i.e., it appears be dynamic process short duration, endowed with quick repair mechanisms. In this review, we consider bacterial, immune, factors responsible for increased permeability both viable bacteria LPS forces, such brushing.

Language: Английский

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Claudin Barriers on the Brink: How Conflicting Tissue and Cellular Priorities Drive IBD Pathogenesis

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(10), P. 8562 - 8562

Published: May 10, 2023

Inflammatory bowel diseases (IBDs) are characterized by acute or chronic recurring inflammation of the intestinal mucosa, often with increasing severity over time. Life-long morbidities and diminishing quality life for IBD patients compel a search better understanding molecular contributors to disease progression. One unifying feature IBDs is failure gut form an effective barrier, core role intercellular complexes called tight junctions. In this review, claudin family junction proteins discussed as they fundamental component barriers. Importantly, expression and/or protein localization altered in IBD, leading supposition that barrier dysfunction exacerbates immune hyperactivity disease. Claudins large transmembrane structural constrain passage ions, water, substances between cells. However, growing evidence suggests non-canonical functions during mucosal homeostasis healing after injury. Therefore, whether claudins participate adaptive pathological responses remains open question. By reviewing current studies, possibility assessed claudins, jack-of-all-trades master none. Potentially, robust wound restitution involve conflicting biophysical phenomena, exposing vulnerabilities tissue-wide frailty IBD.

Language: Английский

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Tight junction membrane proteins regulate the mechanical resistance of the apical junctional complex

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(5)

Published: March 22, 2024

Epithelia must be able to resist mechanical force preserve tissue integrity. While intercellular junctions are known important for the resistance of epithelia, roles tight (TJs) remain established. We previously demonstrated that epithelial cells devoid TJ membrane proteins claudins and JAM-A completely lack TJs exhibit focal breakages their apical junctions. Here, we demonstrate fracture when claudin/JAM-A–deficient undergo spontaneous cell stretching. The junction was accompanied by actin disorganization, polymerization required integrity in cells. Further deletion CAR resulted disruption ZO-1 molecule ordering at junctions, severe defects These results regulate junctional complex

Language: Английский

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Regulation of the Function and Expression of EpCAM

Biomedicines, Journal Year: 2024, Volume and Issue: 12(5), P. 1129 - 1129

Published: May 20, 2024

The epithelial cell adhesion molecule (EpCAM) is a single transmembrane protein on the surface. Given its strong expression cells and cell-derived tumors, EpCAM has been identified as biomarker for circulating tumor (CTCs) exosomes target cancer therapy. As molecule, crystal structure that indicates it forms cis-dimer first then probably trans-tetramer to mediate intercellular adhesion. Through regulated intramembrane proteolysis (RIP), proteolytic fragments are also able regulate multiple signaling pathways, Wnt in particular. Although great progress made, increasingly more findings have revealed context-specific function patterns of their regulation processes, which necessitates further studies determine structure, function, under both physiological pathological conditions, broadening application basic translational research.

Language: Английский

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Damage control of epithelial barrier function in dynamic environments

European Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 103(2), P. 151410 - 151410

Published: April 3, 2024

Epithelial tissues cover the surfaces and lumens of internal organs multicellular animals crucially contribute to environment homeostasis by delineating distinct compartments within body. This vital role is known as epithelial barrier function. cells are arranged like cobblestones intricately bind together form an sheet that upholds this Central restriction solute fluid diffusion through intercellular spaces occluding junctions, tight junctions in vertebrates septate invertebrates. As part tissues, undergo constant renewal, with older being replaced new ones. Simultaneously, tissue undergoes relative rearrangement, elongating, shifting directionally a whole. The movement or shape changes necessitate significant deformation reconnection junctions. Recent advancements have shed light on intricate mechanisms which sustain their function dynamic environments. review aims introduce these noteworthy findings discuss some questions remain unanswered.

Language: Английский

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Tmprss2 maintains epithelial barrier integrity and transepithelial sodium transport

Life Science Alliance, Journal Year: 2024, Volume and Issue: 7(3), P. e202302304 - e202302304

Published: Jan. 3, 2024

The mouse cortical collecting duct cell line presents a tight epithelium with regulated ion and water transport. epithelial sodium channel (ENaC) is localized in the apical membrane constitutes rate-limiting step for entry, thereby enabling transepithelial transport of ions. membrane-bound serine protease Tmprss2 co-expressed alpha subunit ENaC. αENaC gene expression followed expression, absence resulted not only down-regulation protein but also abolished In addition, RNA-sequencing analyses unveiled drastic CAP3/St14, adhesion molecule EpCAM, junction proteins claudin-7 claudin-3 as confirmed by immunohistochemistry. summary, our data clearly demonstrate dual role maintaining ENaC-mediated EpCAM/claudin-7–mediated paracellular barrier; renal mCCD cells becomes leaky. Our working model proposes that acts via CAP3/St14 on EpCAM/claudin-7 complexes through regulating transcription

Language: Английский

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ESCRT-III-dependent adhesive and mechanical changes are triggered by a mechanism detecting alteration of septate junction integrity in Drosophila epithelial cells

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Feb. 2, 2024

Barrier functions of proliferative epithelia are constantly challenged by mechanical and chemical constraints. How respond to cope with disturbances barrier allow tissue integrity maintenance is poorly characterised. Cellular junctions play an important role in this process intracellular traffic contribute their homeostasis. Here, we reveal that, Drosophila pupal notum, alteration the bi- or tricellular septate (SJs) triggers a mechanism two prominent outcomes. On one hand, there increase levels E-cadherin, F-actin, non-muscle myosin II plane adherens junctions. other β-integrin/Vinculin-positive cell contacts reinforced along lateral basal membranes. We found that weakening SJ integrity, caused depletion components, alters ESCRT-III/Vps32/Shrub distribution, reduces degradation instead favours recycling effect extends recycled transmembrane protein cargoes including Crumbs, its effector β-Heavy Spectrin Karst, β-integrin. propose which epithelial cells, upon sensing alterations SJ, reroute function Shrub adjust balance degradation/recycling junctional thereby compensate for junction defects maintain integrity.

Language: Английский

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Molecular determinants of neuroprotection in blood-brain interfaces of the cynomolgus monkey

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 12, 2025

The blood-brain barrier (BBB) formed by the cerebral microvessel endothelium and blood-CSF (BCSFB) choroid plexus epithelium impact bioavailability of drugs endogenous molecules that contribute to neuroinflammatory neurodegenerative diseases. Species specificities in tight junction proteins efflux transporters governing functions these interfaces hamper direct translation pharmacokinetic pathophysiological data from rodents human. We defined molecular composition junctions identified present at BBB BCSFB cynomolgus monkey assess whether this species is a relevant alternative rodents. Choroid plexuses, microvessels, cortex cerebellum were isolated adult monkeys, analysed RT-qPCR immunohistochemistry. Results compared with available literature for rat In monkeys as human, claudin-5 claudin-1, -2, -3 landmark proteins. ABCB1 was strictly associated BBB, ABCC1 predominant BBB. monkey, like differed localization ABCG2 protein choroidal vessels, low expression ABCC4 SLC22A8 presence SLC47A1 BCSFB. While main characteristics brain barriers are common all three species, human share selected claudins not met rat.

Language: Английский

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Tight-junction strand networks and tightness of the epithelial barrier

Microscopy, Journal Year: 2023, Volume and Issue: 72(3), P. 213 - 225

Published: Jan. 28, 2023

Abstract Tight junctions (TJs) are cell–cell junction structures critical for controlling paracellular permeability. On freeze-fracture replica electron microscopy, they appear as a continuous network of fibrils (TJ strands). TJ strands function zippers that create physical barrier against diffusion molecules. The morphology the strand varies greatly between tissues, and in recent years, studies have highlighted mechanisms regulating networks on their relevance to function. In this review, we discuss evidence regarding components creating network. Furthermore, hypothesize how its contributes establishment epithelial barrier.

Language: Английский

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Dexmedetomidine Alleviates Ischemia/Reperfusion-Associated Acute Kidney Injury by Enhancing Autophagic Activity via the α2-AR/AMPK/mTOR Pathway

Frontiers in Bioscience-Landmark, Journal Year: 2023, Volume and Issue: 28(12), P. 323 - 323

Published: Dec. 1, 2023

Background: Dexmedetomidine (DEX) reportedly protects against ischemia-reperfusion (I/R) injury and associated damage to the kidneys, but underlying mechanisms have yet be established. Methods: Unilateral nephrectomy was performed in Wistar rats, remaining kidney clamped for 1 h prior reperfusion establish an experimental model system. These animals were then randomized into Sham, DEX + I/R, ATI (Altepamizole, α2-adrenergic receptor inhibitor) 3-MA (3-methyladenine, autophagy I/R groups. Serum renal function biomarkers, acute (AKI) histopathological scores, serum inflammatory factors, redox markers of autophagic flux, autophagosome numbers assessed. Levels proteins related pathway, including mTOR AMPK, also analyzed. Results: creatinine urea nitrogen levels group significantly elevated over those sham control as AKI cytokine concentrations (IL-6, IL-1β, TNF-α), oxidative stress biomarker malondialdehyde (MDA). All these parameters reduced relative rats. rats exhibited significant decreases flux-related biomarkers controls, while administration partially restored normal flux Acute suppress expression AMPK increasing expression, reversed effects. The beneficial impact on I/R-associated ablated by or administration. Conclusions: analyses provide strong evidence ability protect via α2-AR/AMPK/mTOR pathway-mediated enhancement activity.

Language: Английский

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