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Cornified envelope
About: Cornified envelope is a research topic. Over the lifetime, 647 publications have been published within this topic receiving 35164 citations.
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TL;DR: New insights into the molecular mechanisms and the physiological endpoints of cornification are increasing the understanding of the pathological defects of this unique form of programmed cell death, which is associated with barrier malfunctions and ichthyosis.
Abstract: The epidermis functions as a barrier against the environment by means of several layers of terminally differentiated, dead keratinocytes - the cornified layer, which forms the endpoint of epidermal differentiation and death. The cornified envelope replaces the plasma membrane of differentiating keratinocytes and consists of keratins that are enclosed within an insoluble amalgam of proteins, which are crosslinked by transglutaminases and surrounded by a lipid envelope. New insights into the molecular mechanisms and the physiological endpoints of cornification are increasing our understanding of the pathological defects of this unique form of programmed cell death, which is associated with barrier malfunctions and ichthyosis.
1,567 citations
TL;DR: Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier, which allows the entry of environmental allergens, immunological reaction and inflammation in atopic dermatitis.
Abstract: The skin forms an effective barrier between the organism and the environment preventing invasion of pathogens and fending off chemical and physical assaults, as well as the unregulated loss of water and solutes In this review we provide an overview of several components of the physical barrier, explaining how barrier function is regulated and altered in dermatoses The physical barrier is mainly localized in the stratum corneum (SC) and consists of protein-enriched cells (corneocytes with cornified envelope and cytoskeletal elements, as well as corneodesmosomes) and lipid-enriched intercellular domains The nucleated epidermis also contributes to the barrier through tight, gap and adherens junctions, as well as through desmosomes and cytoskeletal elements During epidermal differentiation lipids are synthesized in the keratinocytes and extruded into the extracellular domains, where they form extracellular lipid-enriched layers The cornified cell envelope, a tough protein/lipid polymer structure, resides below the cytoplasmic membrane on the exterior of the corneocytes Ceramides A and B are covalently bound to cornified envelope proteins and form the backbone for the subsequent addition of free ceramides, free fatty acids and cholesterol in the SC Filaggrin is cross-linked to the cornified envelope and aggregates keratin filaments into macrofibrils Formation and maintenance of barrier function is influenced by cytokines, 3',5'-cyclic adenosine monophosphate and calcium Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier, which allows the entry of environmental allergens, immunological reaction and inflammation in atopic dermatitis A disturbed skin barrier is important for the pathogenesis of contact dermatitis, ichthyosis, psoriasis and atopic dermatitis
1,495 citations
TL;DR: More sophisticated understanding of epidermal barrier function will lead to more rational therapy of a host of skin conditions in which the barrier is impaired, current work has focused on developing a more physiologic mix of lipids for topical application to skin.
1,026 citations
TL;DR: Late in the terminal differentiation of epidermis and cultured epidermal cells, a protein envelope located beneath the plasma membrane becomes cross-linked by cellular transglutaminase, and cannot be extracted from keratinocytes after their envelopes have become cross- linked.
771 citations
TL;DR: It is shown here that Kruppel-like factor 4 (Klf4, encoded by the gene Klf4), highly expressed in the differentiating layers of epidermis, is both vital to and selective for barrier acquisition, and provides new insights into transcriptional governance of barrier function.
Abstract: Located at the interface between body and environment, the epidermis must protect the body against toxic agents and dehydration, and protect itself against physical and mechanical stresses Acquired just before birth and at the last stage of epidermal differentiation, the skin's proteinaceous/lipid barrier creates a surface seal essential for protecting animals against microbial infections and dehydration We show here that Kruppel-like factor 4 (Klf4, encoded by the gene Klf4), highly expressed in the differentiating layers of epidermis, is both vital to and selective for barrier acquisition Klf4-/- mice die shortly after birth due to loss of skin barrier function, as measured by penetration of external dyes and rapid loss of body fluids The defect was not corrected by grafting of Klf4-/- skin onto nude mice Loss of the barrier occurs without morphological and biochemical alterations to the well-known structural features of epidermis that are essential for mechanical integrity Instead, late-stage differentiation structures are selectively perturbed, including the cornified envelope, a likely scaffold for lipid organization Using suppressive subtractive hybridization, we identified three transcripts encoding cornified envelope proteins with altered expression in the absence of Klf4 Sprr2a is one, and is the only epidermal gene whose promoter is known to possess a functional Klf4 binding site Our studies provide new insights into transcriptional governance of barrier function, and pave the way for unravelling the molecular events that orchestrate this essential process
758 citations