Tight junctions in the stratum corneum explain spatial differences in corneodesmosome degradation

Abstract

To maintain stratum corneum integrity while simultaneously desquamating at a steady rate, degradation of corneodesmosomes must proceed in a controlled manner. It is unknown why corneodesmosomes are present only at the cell periphery in the upper stratum corneum. To explore this, we studied distributions of three major corneodesmosomal components, corneodesmosin, desmoglein 1 and desmocollin 1 in normal adult human epidermis. Immunofluorescent microscopy studies of skin surface corneocytes detected all three components only at the cell edges. Immunoelectron microscopy revealed selective loss of these components at the central areas starting from the deep cornified layers. We hypothesized that tight junctions (TJs) formed in the superficial granular layer may prevent protease access by functioning as a barrier between the peripheral and the central intercellular spaces in the stratum corneum. Ultrastructural examination demonstrated TJs up to the junctions between the seventh and the eighth deepest cornified layers. Immunoelectron microscopy also detected clusters of occludin and claudin-1 immunolabels at the cell periphery, and kallikrein 7 immunolabels outside of TJs in the lower cornified layers. With colloidal lanthanum nitrate perfusion assay of stripped stratum corneum, the tracer was excluded from TJ domains. Taken together, we propose that TJs inhibit access of proteases to the peripheral corneodesmosomes forming the structural basis for the basket-weave-like appearance of the stratum corneum.

Development of a Novel Approach to Studying Corneodesmosomes and Stratum Corneum Adhesion: Extending Knowledge on the Pathophysiology of Sensitive Skin

“…Higher levels of DSG1 in the first tape strip correlated with higher levels of TEWL ( r = 0.516, p < 0.01) [7]. In our study, we could not show a clear change in distribution pattern of DSG1 in the corneocytes, hence we observed a decrease in expression with depth.…”

“…Naoe et al [33] and Igawa et al [7] proved that the distribution of DSG1 in the upper layers is peripheral, whereas in the deepest layers of the SC DSG1 it is distributed over the entire corneocyte surface. Higher levels of DSG1 in the first tape strip correlated with higher levels of TEWL ( r = 0.516, p < 0.01) [7].…”

“…The ceramides are an important determinant of the unusual physical properties of these SC lipid bilayers [3-5]. Via cell-cell junctions, the corneocytes are connected to each other as corneodesmosomes, where a highly controlled degradation of these corneodesmosomes results in desquamation [6, 7]. The major components of corneodesmosomes are corneodesmosin, desmoglein 1 (DSG1), and desmocollin 1.…”

Desquamation: It Is Almost All About Proteases

“…Therefore, peripheral corneodesmosomes remain relatively intact up to the skin surface. Indeed, Igawa et al [ 48 ] observed persistence of these TJ-like structures up to the eighth deepest cornifi ed layers. Immunoelectron microscopy also detected clusters of the TJ marker proteins occludin and claudin-1 at the corneocyte periphery, whereas kallikrein 7 (KLK7) immunolabeling was found outside of TJ-derived structures in the extracellular space of the lower cornifi ed layers.…”

The Role of Tight Junctions and Aquaporins in Skin Dryness

“…Lastly, Cldn-1 and Ocln, as well as TJ-related structures, were also found in the lower layers of SC and were suggested to play a role in protection of corneodesmosomes at the lateral plasma membranes from precocious degradation, therefore contributing to orchestrated desquamation [ 35,47,36 ] .…”