Abstract
Epidermal barrier integrity could be influenced by various factors involved in epidermal cell differentiation and proliferation, cell–cell adhesion, and skin lipids. Dysfunction of this barrier can cause skin disorders, including eczema. Inversely, eczema can also damage the epidermal barrier. These interactions through vicious cycles make the mechanism complicated in connection with other mechanisms, particularly immunologic responses. In this article, the molecular mechanisms concerning epidermal barrier abnormalities are reviewed in terms of the following categories: epidermal calcium gradients, filaggrin, cornified envelopes, desquamation, and skin lipids. Mechanisms linked to ichthyoses, atopic dermatitis without exacerbation or lesion, and early time of experimental irritation were included. On the other hand, the mechanism associated with epidermal barrier abnormalities resulting from preceding skin disorders was excluded. The molecular mechanism involved in epidermal barrier dysfunction has been mostly episodic. Some mechanisms have been identified in cultured cells or animal models. Nonetheless, research into the relationship between the causative molecules has been gradually increasing. Further evidence-based systematic data of target molecules and their interactions would probably be helpful for a better understanding of the molecular mechanism underlying the dysfunction of the epidermal barrier.
Highlights
The skin functions as a barrier against the environment by protecting from mechanical insults, microorganisms, chemicals, and allergens
This review shows that abnormalities in factors involved in epidermal barrier integrity, such as epidermal calcium gradients, filaggrin, cornified envelopes, desquamation of corneodesmosomes, and skin lipids, are associated with epidermal barrier dysfunction
Atopic dermatitis without exacerbation or lesion, and early time of experimental irritation could be considered as causes and not results of skin barrier dysfunction
Summary
The skin functions as a barrier against the environment by protecting from mechanical insults, microorganisms, chemicals, and allergens. The parameters include transepidermal water loss, electrical conductance, surface pH, lipid composition, skin blood flow, skin color, and skin thickness [5,6]. These skin diseases could reversely damage the skin barrier, thereby resulting in a vicious cycle [7]. Causative mechanisms involved in primary epidermal barrier dysfunction might be more valuable for the prevention of skin diseases induced by barrier abnormalities. This review covers molecular mechanisms of epidermal barrier dysfunction as primary abnormalities by focusing on the causative factors of skin diseases (atopic dermatitis and ichthyoses) and experimental skin conditions (tape stripping and irritant application) associated with skin barrier abnormalities
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