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Tissue Barriers

Kinga Duszyc, Guillermo A Gomez, Kate Schroder, Matthew J Sweet, Alpha S Yap
Apoptosis is a ubiquitous mode of programmed cell death that is found in healthy organs and can be stimulated by many toxic stresses. When it occurs in epithelia, apoptosis presents major challenges to tissue integrity. Apoptotic corpses can promote inflammatory and autoimmune responses if they are retained, and the cellular fragmentation that accompanies apoptosis can potentially compromise the epithelial barrier. Here we discuss 2 homeostatic mechanisms that allow epithelia to circumvent these potential risks: clearance of apoptotic corpses by professional and non-professional phagocytes and physical expulsion of apoptotic cells by apical extrusion...
June 28, 2017: Tissue Barriers
Alan R Parrish
The epithelium has many critical roles in homeostasis, including an essential responsibility in establishing tissue barriers. In addition to the fundamental role in separating internal from external environment, epithelial barriers maintain nutrient, fluid, electrolyte and metabolic waste balance in multiple organs. While, by definition, barrier function is conserved, the structure of the epithelium varies across organs. For example, the skin barrier is a squamous layer of cells with distinct structural features, while the lung barrier is composed of a very thin single cell to minimize diffusion space...
June 26, 2017: Tissue Barriers
Reitaro Tokumasu, Atsushi Tamura, Sachiko Tsukita
There are many types of biologic compartments in the body. Tight junctions (TJs) function to create a dynamic paracellular barrier to separate these compartments and maintain homeostasis. The TJ component claudin-1 is the major transmembrane protein responsible for forming the paracellular barrier in the epidermis; other claudins in the epidermis include claudin-3, -4, -12, -23 and -25. Accumulating evidence points to a relationship between claudin-1 and skin diseases; for example, a decrease in claudin-1 is reported in human atopic dermatitis...
June 19, 2017: Tissue Barriers
Melissa Crawford, Lina Dagnino
The skin of mammals and other terrestrial vertebrates protects the organism against the external environment, preventing heat, water and electrolyte loss, as well as entry of chemicals and pathogens. Impairments in the epidermal permeability barrier function are associated with the genesis and/or progression of a variety of pathological conditions, including genetic inflammatory diseases, microbial and viral infections, and photodamage induced by UV radiation. In mammals, the outside-in epidermal permeability barrier is provided by the joint action of the outermost cornified layer, together with assembled tight junctions in granular keratinocytes found in the layers underneath...
June 13, 2017: Tissue Barriers
Kathryn L Pothoven, Robert P Schleimer
Mucosal epithelium maintains tissue homeostasis through many processes, including epithelial barrier function, which separates the environment from the tissue. The barrier hypothesis of type 2 inflammatory disease postulates that epithelial and epidermal barrier dysfunction, which cause inappropriate exposure to the environment, can result in allergic sensitization and development of type 2 inflammatory disease. The restoration of barrier dysfunction once it's lost, or the prevention of barrier dysfunction, have the potential to be exciting new therapeutic strategies for the treatment of type 2 inflammatory disease...
June 13, 2017: Tissue Barriers
Carla J Ramos, David A Antonetti
Maintenance and regulation of the vascular endothelial cell junctional complex is critical for proper barrier function of the blood-brain barrier (BBB) and the highly related blood-retinal barrier (BRB) that help maintain proper neuronal environment. Recent research has demonstrated that the junctional complex is actively maintained and can be dynamically regulated. Studies focusing on the mechanisms of barrier formation, maintenance, and barrier disruption have been of interest to understanding development of the BBB and BRB and identifying a means for therapeutic intervention for diseases ranging from brain tumors and dementia to blinding eye diseases...
June 9, 2017: Tissue Barriers
Ming-Fang Wu, Chen-Yi Liao, Ling-Yi Wang, Jinghua Tsai Chang
The role of Slit/Robo signaling has extended from initial axon repulsion in the developing nervous system to organ morphogenesis, cancer development and angiogenesis. Slit/Robo signaling regulates similar pathways within these processes. Slit/Robo ensures the homeostasis of the dynamic interaction between cell-cell and cell-matrix interactions. The dysregulation of Slit/Robo signaling damages the tissue barrier, resulting in developmental abnormalities or disease. Here, we summarize how Slit/Robo controls kidney morphogenesis and describe the dual roles of Slit/Robo signaling in the regulation of tumorigenesis and angiogenesis...
April 3, 2017: Tissue Barriers
Evan W Weber, William A Muller
Transient receptor potential (TRP) channels are a ubiquitously expressed multi-family group of cation channels that are critical to signaling events in many tissues. Their roles have been documented in many physiologic and pathologic conditions. Nevertheless, direct studies of their roles in maintain barrier function in endothelial and epithelia are relatively infrequent. This seems somewhat surprising considering that calcium ion concentrations are known to regulate barrier function. This short review provides an introduction to TRP channels and reviews some of the work in which investigators directly studied the role of TRP channels in endothelial permeability to electric current, solute, or leukocytes during the inflammatory response...
April 3, 2017: Tissue Barriers
Susan J Hagen
Tight junctions form a barrier to the diffusion of apical and basolateral membrane proteins thus regulating membrane polarity. They also regulate the paracellular movement of ions and water across epithelial and endothelial cells so that functionally they constitute an important permselective barrier. Permselectivity at tight junctions is regulated by claudins, which confer anion or cation permeability, and tightness or leakiness, by forming several highly regulated pores within the apical tight junction complex...
April 3, 2017: Tissue Barriers
Alan S L Yu
Paracellular transport of solutes and water accompanies transcellular transport across epithelial barriers and together they serve to maintain internal body composition. However, whether paracellular transport is necessary and why it evolved is unknown. In this commentary I discuss our recent studies to address this question in the proximal tubule of the kidney. Paracellular reabsorption of sodium occurs in the proximal tubule and is mediated by claudin-2. However, deletion of claudin-2 in mice does not affect whole kidney sodium excretion because it can be completely compensated by downtream transcellular transport mechanisms...
April 3, 2017: Tissue Barriers
Agnes Weth, Carsten Dippl, Yasmin Striedner, Irene Tiemann-Boege, Yana Vereshchaga, Nikola Golenhofen, Britta Bartelt-Kirbach, Werner Baumgartner
In the intestine water has to be reabsorbed from the chymus across the intestinal epithelium. The osmolarity within the lumen is subjected to high variations meaning that water transport often has to take place against osmotic gradients. It has been hypothesized that LI-cadherin is important in this process by keeping the intercellular cleft narrow facilitating the buildup of an osmotic gradient allowing water reabsorption. LI-cadherin is exceptional among the cadherin superfamily with respect to its localization along the lateral plasma membrane of epithelial cells being excluded from adherens junction...
April 3, 2017: Tissue Barriers
Derek M McKay, Adam Shute, Fernando Lopes
Approximately one-sixth of the worlds' population is infected with helminths and this class of parasite takes a major toll on domestic livestock. The majority of species of parasitic helminth that infect mammals live in the gut (the only niche for tapeworms) where they contact the hosts' epithelial cells. Here, the helminth-intestinal epithelial interface is reviewed in terms of the impact on, and regulation of epithelial barrier function, both intrinsic (epithelial permeability) and extrinsic (mucin, bacterial peptides, commensal bacteria) elements of the barrier...
January 2, 2017: Tissue Barriers
Thibault Allain, Christina B Amat, Jean-Paul Motta, Anna Manko, André G Buret
Understanding how intestinal enteropathogens cause acute and chronic alterations has direct animal and human health perspectives. Significant advances have been made on this field by studies focusing on the dynamic crosstalk between the intestinal protozoan parasite model Giardia duodenalis and the host intestinal mucosa. The concept of intestinal barrier function is of the highest importance in the context of many gastrointestinal diseases such as infectious enteritis, inflammatory bowel disease, and post-infectious gastrointestinal disorders...
January 2, 2017: Tissue Barriers
Mark R Gillrie, May Ho
Plasmodial species are protozoan parasites that infect erythrocytes. As such, they are in close contact with microvascular endothelium for most of the life cycle in the mammalian host. The host-parasite interactions of this stage of the infection are responsible for the clinical manifestations of the disease that range from a mild febrile illness to severe and frequently fatal syndromes such as cerebral malaria and multi-organ failure. Plasmodium falciparum, the causative agent of the most severe form of malaria, is particularly predisposed to modulating endothelial function through either direct adhesion to endothelial receptor molecules, or by releasing potent host and parasite products that can stimulate endothelial activation and/or disrupt barrier function...
January 2, 2017: Tissue Barriers
Emily J Jones, Tamas Korcsmaros, Simon R Carding
Toxoplasma gondii is a ubiquitous parasite and a prevalent food-borne parasitic pathogen. Infection of the host occurs principally through oral consumption of contaminated food and water with the gastrointestinal tract being the primary route for entry into the host. To promote infection, T. gondii has evolved highly specialized strategies for rapid traversal of the single cell thick intestinal epithelial barrier. Parasite transmigration via the paracellular pathway between adjacent cells enables parasite dissemination to secondary sites of infection where chronic infection of muscle and brain tissue is established...
January 2, 2017: Tissue Barriers
Steve Cornick, Kris Chadee
Entamoeba histolytica (Eh) is the protozoan parasite responsible for intestinal amebiasis and interacts dynamically with the host intestinal epithelium during disease pathogenesis. A multifaceted pathogenesis profile accounts for why 90% of individuals infected with Eh are largely asymptomatic. For 100 millions individuals that are infected each year, key interactions within the intestinal mucosa dictate disease susceptibility. The ability for Eh to induce amebic colitis and disseminate into extraintestinal organs depends on the parasite competing with indigenous bacteria and overcoming the mucus barrier, binding to host cells inducing their cell death, invasion through the mucosa and outsmarting the immune system...
January 2, 2017: Tissue Barriers
Loukia N Lili, Attila E Farkas, Christian Gerner-Smidt, Christian E Overgaard, Carlos S Moreno, Charles A Parkos, Christopher T Capaldo, Asma Nusrat
Colonic enterocytes form a rapidly renewing epithelium and barrier to luminal antigens. During renewal, coordinated expression of the claudin family of genes is vital to maintain the epithelial barrier. Disruption of this process contributes to barrier compromise and mucosal inflammatory diseases. However, little is known about the regulation of this critical aspect of epithelial cell differentiation. In order to identify claudin regulatory factors we utilized high-throughput gene microarrays and correlation analyses...
July 2016: Tissue Barriers
Valentina Volynets, Andreas Rings, Gyöngyi Bárdos, Maureen J Ostaff, Jan Wehkamp, Stephan C Bischoff
The intestinal barrier is gaining increasing attention because it is related to intestinal homeostasis and disease. Different parameters have been used in the past to assess intestinal barrier functions in experimental studies; however most of them are poorly defined in healthy mice. Here, we compared a number of barrier markers in healthy mice, established normal values and correlations. In 48 mice (24 C57BL/6J, 24 BALB/cJ background), we measured mucus thickness, and expression of mucin-2, α-defensin-1 and -4, zonula occludens-1, occludin, junctional adhesion molecule-A, claudin-1, 2 and -5...
July 2016: Tissue Barriers
Alison R Hill, Jessica E Donaldson, Cornelia Blume, Natalie Smithers, Liku Tezera, Kamran Tariq, Patrick Dennison, Hitasha Rupani, Matthew J Edwards, Peter H Howarth, Christopher Grainge, Donna E Davies, Emily J Swindle
The bronchial epithelium and underlying fibroblasts form an epithelial mesenchymal trophic unit (EMTU) which controls the airway microenvironment. We hypothesized that cell-cell communication within the EMTU propagates and amplifies the innate immune response to respiratory viral infections. EMTU co-culture models incorporating polarized (16HBE14o-) or differentiated primary human bronchial epithelial cells (HBECs) and fibroblasts were challenged with double-stranded RNA (dsRNA) or rhinovirus. In the polarized EMTU model, dsRNA affected ionic but not macromolecular permeability or cell viability...
July 2016: Tissue Barriers
Hillary J Haws, Melissa A McNeil, Marc D H Hansen
Epithelial tissues use adherens junctions to maintain tight interactions and coordinate cellular activities. Adherens junctions are remodeled during epithelial morphogenesis, including instances of epithelial-mesenchymal transition, or EMT, wherein individual cells detach from the tissue and migrate as individual cells. EMT has been recapitulated by growth factor induction of epithelial scattering in cell culture. In culture systems, cells undergo a highly reproducible series of cell morphology changes, most notably cell spreading followed by cellular compaction and cell migration...
July 2016: Tissue Barriers
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