Adherens Junctions, Desmosomes and Tight Junctions in Epidermal Barrier Function

Abstract

The skin is an indispensable barrier which protects the body from the uncontrolled loss of water and solutes as well as from chemical and physical assaults and the invasion of pathogens. In recent years several studies have suggested an important role of intercellular junctions for the barrier function of the epidermis. In this review we summarize our knowledge of the impact of adherens junctions, (corneo)-desmosomes and tight junctions on barrier function of the skin.

Desquamation: It Is Almost All About Proteases

“…The differentiation-dependent composition of desmosomes coincides with the increase of their mechanical stability. In the basal layer, desmosomes are infrequent and small; their size and number rise signifi cantly in the spinous layers and decrease subsequently in the granular compartment [ 14 ] . Desmosomes have round or oval, button-like structures with a diameter of 0.2-1 m m [ 15 ] .…”

“…In the same way DSC3 is replaced by DSC1 (Fig. 11.3 ) [ 14 ] . Thus, DSC1, DSG1, and DSG4 are strongly associated with terminally differentiating layers, while the remaining isoforms are associated with the lower, proliferating cell layers, suggesting that this differentiation-specifi c pattern may regulate epidermal development and differentiation [ 23 ] .…”

“…Reasons for the preferential digestion of nonperipheral corneodesmosomes may include: A higher impact of shearing forces on junc-• tions between fl at rigid surfaces, when applied to the skin or naturally occurring during changes of the corneocyte volume due to variations in the water content Easier access for the enzymes, displaced • by self-organizing lipid bilayers, when compared to the convoluted lateral intercorneocyte spaces An additional protection from degradation of • the peripheral junctions by supplementary structures, like remnants of strategically placed tight junctions cross-linked to CEs at the periphery of corneocytes [ 14 ] A change in frequency and size of corneodesmosomes is obvious between the deeper and the more superfi cial layers of the SC. On nonpalmoplantar SC, corneodesmosomes occupy approximately 30% of the cell surface in the stratum compactum, but represent less than 7% of the cell surface in the stratum disjunctum [ 29 ] .…”

Molecular Organization of the Lipid Matrix in Stratum Corneum and Its Relevance for the Protective Functions of Human Skin

“…The extent of lipids participating in OR phases correlates well with the degree of integrity (measured by the change of basal TEWL following tape-stripping) but does not correlate with the degree of cohesion (measured by the protein content of the tapes) in healthy human skin in vivo [ 145 ] . Most probably, this observation refl ects a different, indirect mechanism by which the lipid molecular organization can impact the integrity and cohesion of SC: by enabling the diffusion of the SC enzymes and of their respective activators and inhibitors to their substrates [ 105,136 ] , such as proteolytic enzymes necessary for degradation of the corneodesmosomes [ 111,146 ] and lipid hydrolases necessary to transform precursors secreted form the LB into SC components [ 104 ] .…”

“…The correlation between the two parameters observed in normal, healthy skin indicates that to reduce the TEWL by 5 g/m 2 h, the content of OR phases has to increase by approximately 50% [ 76 ] ; depending on the degree of damage to the SC barrier for water, it is possible that the most effi cient products for improving the SC moisturization would be those that make use of all three mechanismswater retention, external occlusion, and internal occlusion -acting simultaneously. It is also important to consider that the content of OR phase is not the only factor contributing to TEWL: together with the water permeability of the SC lipid matrix, the presence of fully matured corneocytes [ 111,146 ] and water-retaining constituents of NMF [ 156 ] also contribute to the sustaining of SC hydration. Furthermore, it is generally accepted that the presence of the LPP is important for maintaining an effi cient barrier to the transport of exogenous chemicals across the SC.…”