Abstract
One of the most important functions of skin is to act as a protective barrier. To fulfill this role, the structural integrity of the skin depends on the dermal-epidermal junction—a complex network of extracellular matrix macromolecules that connect the outer epidermal layer to the underlying dermis. This junction provides both a structural support to keratinocytes and a specific niche that mediates signals influencing their behavior. It displays a distinctive microarchitecture characterized by an undulating pattern, strengthening dermal-epidermal connectivity and crosstalk. The optimal stiffness arising from the overall molecular organization, together with characteristic anchoring complexes, keeps the dermis and epidermis layers extremely well connected and capable of proper epidermal renewal and regeneration. Due to intrinsic and extrinsic factors, a large number of structural and biological changes accompany skin aging. These changes progressively weaken the dermal–epidermal junction substructure and affect its functions, contributing to the gradual decline in overall skin physiology. Most changes involve reduced turnover or altered enzymatic or non-enzymatic post-translational modifications, compromising the mechanical properties of matrix components and cells. This review combines recent and older data on organization of the dermal-epidermal junction, its mechanical properties and role in mechanotransduction, its involvement in regeneration, and its fate during the aging process.
Highlights
One of the most important functions of skin is to act as a protective barrier
By experimentally imposing substrate deformations similar in magnitude and rate of deformation to those that can be generated by an evolving multicellular aggregate of keratinocytes, the authors further revealed that isolated keratinocytes favored a course that vectorially aligned with the direction of substrate deformation, using a signaling pathway involving Rho-associated kinase (ROCK) [132]
The dermal–epidermal junction (DEJ) primary structural elements consist of two polymeric networks comprising laminin and collagen IV, which are primarily interconnected by nidogen and perlecan [3,14]
Summary
One of the most important functions of skin is to act as a protective barrier. To fulfill this role, the structural integrity of the skin depends on the basement membrane—a complex network of extracellular matrix (ECM) macromolecules that connect the outer epidermal layer to the underlying dermis. The DEJ provides a highly dynamic microenvironment to the keratinocytes by participating in epidermal renewal under physiological conditions and taking part in repair processes during skin healing [13,14,15,16] In both scenarios, the DEJ serves as an adhesive scaffold, and its constituents may be part of signaling events that vary depending on maturation processes driven by ECM-modifying enzymes [17,18]. Through binding and sequestering of soluble growth factors in the presence of appropriate cell-mediated forces or proteolytic degradation, basement membranes can enable spatial-temporal regulation of receptor–ligand interactions. These ECMs can generate and transduce mechanical signals. Through interactions with cell surface receptors, these ECMs modulate a remarkably wide range of signaling processes
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