Contributions of Myosin Light Chain Kinase to Regulation of Epithelial Paracellular Permeability and Mucosal Homeostasis

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(3), P. 993 - 993

Published: Feb. 3, 2020

Intestinal barrier function is required for the maintenance of mucosal homeostasis. Barrier dysfunction thought to promote progression both intestinal and systemic diseases. In many cases, this loss reflects increased permeability paracellular tight junction as a consequence myosin light chain kinase (MLCK) activation II regulatory (MLC) phosphorylation. Although some details about MLCK remain be defined, it clear that triggers perijunctional actomyosin ring (PAMR) contraction leads molecular reorganization structure composition, including occludin endocytosis. disease states, process can triggered by pro-inflammatory cytokines tumor necrosis factor-α (TNF), interleukin-1β (IL-1β), several related molecules. Of these, TNF has been studied in greatest detail known activate long transcription, expression, enzymatic activity, recruitment PAMR. Unfortunately, toxicities associated with inhibition expression or activity make these unsuitable therapeutic targets. Recent work has, however, identified small molecule prevents MLCK1 PAMR without inhibiting function. This molecule, termed Divertin, restores after TNF-induced experimental chronic inflammatory bowel disease.

Language: Английский

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RhoA Mediates Epithelial Cell Shape Changes via Mechanosensitive Endocytosis

Developmental Cell, Journal Year: 2019, Volume and Issue: 52(2), P. 152 - 166.e5

Published: Dec. 26, 2019

Language: Английский

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Theory of mechanochemical patterning and optimal migration in cell monolayers

Nature Physics, Journal Year: 2020, Volume and Issue: 17(2), P. 267 - 274

Published: Sept. 28, 2020

Language: Английский

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Abl and Canoe/Afadin mediate mechanotransduction at tricellular junctions

Science, Journal Year: 2020, Volume and Issue: 370(6520)

Published: Nov. 27, 2020

Tension where multiple cells meet Cells exist in varying environments and must respond to specific stimuli. During development, epithelial need rapidly reorganize under tension without compromising integrity. Yu et al. demonstrate that Drosophila achieve this by transiently stabilizing adhesion at tricellular junctions three (see the Perspective Raghavan Vasioukhin). The conserved regulator Canoe/Afadin is recruited within seconds dissociates when released through a mechanism requires Abl-dependent tyrosine phosphorylation. These results identify an vivo mechanotransduction pathway dynamically couples with physiological forces, allowing modulate their behavior response mechanical changes environment. Science , issue p. eaba5528 ; see also 1036

Language: Английский

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Tight Junctions in Cell Proliferation

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(23), P. 5972 - 5972

Published: Nov. 27, 2019

Tight junction (TJ) proteins form a continuous intercellular network creating barrier with selective regulation of water, ion, and solutes across endothelial, epithelial, glial tissues. TJ include the claudin family that confers properties, members MARVEL contribute to regulation, JAM molecules, which regulate organization diapedesis. In addition, membrane-associated such as MAGUK members, i.e., zonula occludens, scaffold linking transmembrane both cell signaling molecules cytoskeleton. Most studies have focused on contribution cell-cell adhesion tissue properties. However, recent reveal that, similar adherens proteins, control proliferation. this review, we will summarize discuss specific role in epithelial endothelial some cases, act reservoir critical cycle modulators, by binding regulating their nuclear access, while other junctional are located at cellular organelles, transcription Collectively, these proliferation differentiation required for forming maintaining barrier.

Language: Английский

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Active biomaterials for mechanobiology

Biomaterials, Journal Year: 2020, Volume and Issue: 267, P. 120497 - 120497

Published: Oct. 26, 2020

Language: Английский

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Sidekick Is a Key Component of Tricellular Adherens Junctions that Acts to Resolve Cell Rearrangements

Developmental Cell, Journal Year: 2019, Volume and Issue: 50(3), P. 313 - 326.e5

Published: July 25, 2019

Language: Английский

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Mouse embryo geometry drives formation of robust signaling gradients through receptor localization

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Oct. 4, 2019

Abstract Morphogen signals are essential for cell fate specification during embryogenesis. Some receptors that sense these morphogens known to localize only the apical or basolateral membrane of polarized lines in vitro. How such localization affects morphogen sensing and patterning developing embryo remains unknown. Here, we show formation a robust BMP signaling gradient early mouse depends on restricted, receptors. The mis-localization results ectopic epiblast vivo. With evidence from mathematical modeling, human embryonic stem cells vitro, embryos vivo, find geometric compartmentalization ligands creates is buffered against fluctuations. Our demonstrate importance receptor geometry shaping

Language: Английский

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Apoptotic extracellular vesicles are metabolized regulators nurturing the skin and hair

Bioactive Materials, Journal Year: 2022, Volume and Issue: 19, P. 626 - 641

Published: May 11, 2022

Over 300 billion of cells die every day in the human body, producing a large number endogenous apoptotic extracellular vesicles (apoEVs). Also, allogenic stem cell transplantation, commonly used therapeutic approach current clinical practice, generates exogenous apoEVs. It is well known that phagocytic engulf and digest apoEVs to maintain body's homeostasis. In this study, we show fraction metabolized integumentary skin hair follicles. Mechanistically, activate Wnt/β-catenin pathway facilitate their metabolism wave-like pattern. The migration enhanced by treadmill exercise inhibited tail suspension, which associated with mechanical force-regulated expression DKK1 circulation. Furthermore, promote wound healing growth via activation follicle mesenchymal cells. This study reveals previously unrecognized metabolic opens new avenue for exploring apoEV-based therapy disorders.

Language: Английский

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The urothelium: a multi-faceted barrier against a harsh environment

Mucosal Immunology, Journal Year: 2022, Volume and Issue: 15(6), P. 1127 - 1142

Published: Sept. 30, 2022

All mucosal surfaces must deal with the challenge of exposure to outside world. The urothelium is a highly specialized layer stratified epithelial cells lining inner surface urinary bladder, gruelling environment involving significant stretch forces, osmotic and hydrostatic pressures, toxic substances, microbial invasion. bladder plays an important barrier role allows accommodation expulsion large volumes urine without permitting components diffuse across. made up three cell types, basal, intermediate, umbrella cells, whose functions aid in bladder's mission. In this review, we summarize recent insights into urothelial structure, function, development, regeneration, particular formation maintenance. We briefly review diseases which involve discuss current human vitro models as complement traditional animal studies.

Language: Английский

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