Abstract
Mammalian epidermis is a striking example of the role of lipids in tissue biology. In this stratified epithelium, highly specialized structures are formed that leverage the hydrophobic properties of lipids to form an impermeable barrier and protect the humid internal environment of the body from the dry outside. This is achieved through tightly regulated lipid synthesis that generates the molecular species unique to the tissue. Beyond their fundamental structural role, lipids are involved in the active protection of the body from external insults. Lipid species present on the surface of the body possess antimicrobial activity and directly contribute to shaping the commensal microbiota. Lipids belonging to a variety of classes are also involved in the signaling events that modulate the immune responses to environmental stress as well as differentiation of the epidermal keratinocytes themselves. Recently, high-resolution methods are beginning to provide evidence for the involvement of newly identified specific lipid molecules in the regulation of epidermal homeostasis. In this review we give an overview of the wide range of biological functions of mammalian epidermal lipids.
Highlights
The evolution of an impermeable barrier that could preserve the internal aqueous environment of the body away from water in ancestral reptiles was one of the most important events that allowed the colonization of dry land by vertebrates
The journey of a keratinocyte from basal layer stem cell to stratum corneum corneocyte is influenced by several cellular signaling pathways that control the balance between proliferation and differentiation, exit from the stem cell compartment and progression through the epidermal layers
Binding to LPA1 or LPA5 instead leads to an increase in the differentiation marker pro-filaggrin and alteration of cellular morphology, signaling via Gα12/13 to RhoA-ROCK and activating Serum Response Factor (SRF) (Figure 6)
Summary
The evolution of an impermeable barrier that could preserve the internal aqueous environment of the body away from water in ancestral reptiles was one of the most important events that allowed the colonization of dry land by vertebrates. Lipids from numerous different classes and cellular origins can work as paracrine or autocrine mediators through cellsurface receptors to help determine the type of adaptive immune response that is triggered after an external stimulus perturbs the physiological equilibrium of the skin or to intervene in the regulation of epidermal cell behavior (Figure 4).
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