Lipopenia and Skin Barrier Abnormalities in DGAT2-deficient Mice*
Dgat2-deficient mice are lipopenic and die soon after birth, apparently from profound reductions in substrates for energy metabolism and from impaired permeability barrier function in the skin, supporting the hypothesis that the two enzymes play fundamentally different roles in mammalian triglyceride metabolism.
Stratum corneum defensive functions: an integrated view.
- P. Elias
- PsychologyJournal of Investigative Dermatology
- 1 August 2005
The ways in which the multiple defensive functions of the SC are linked and interrelated, either by their shared localization or by common biochemical processes are explored; how they are co-regulated in response to specific stressors; and how alterations in one defensive function impact other protective functions.
Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema
It is shown that the common filaggrin (FLG) null mutations that cause ichthyosis vulgaris and predispose to eczema and secondary allergic diseases are ancestral variants carried on conserved haplotypes, and a strategy for full sequencing of this large, highly repetitive gene is reported.
A Homolog of Drosophila grainy head Is Essential for Epidermal Integrity in Mice
It is reported that formation and maintenance of the epidermal barrier in mice are dependent on a mammalian homolog of grainy head, Grainy head-like 3, which suggests that the functional mechanisms involving protein cross-linking that maintain the epidersmal barrier and induce tissue repair are conserved across 700 million years of evolution.
Structural and lipid biochemical correlates of the epidermal permeability barrier.
Spink5-deficient mice mimic Netherton syndrome through degradation of desmoglein 1 by epidermal protease hyperactivity
This work identifies LEKTI as a key regulator of epidermal protease activity and degradation of desmoglein 1 as the primary pathogenic event in Netherton syndrome.
The skin barrier as an innate immune element
- P. Elias
- BiologySeminars in Immunopathology
- 30 March 2007
Permeability and antimicrobial function are both co-regulated and interdependent, overlapping through the dual activities of their lipid/protein constituents, and the key role of epithelial structure in antimicrobial defense is emphasized.
Ionic calcium reservoirs in mammalian epidermis: ultrastructural localization by ion-capture cytochemistry.
The striking intercellular Ca++ accumulation in the mid granular layer, coupled with Ca++ influx in the upper granular layers, supports the view that changes in intracellular Ca++ may regulate epidermal differentiation and suggests that divalent cations may contribute to both lamellar body secretion and to the formation of intercorneocyte membrane bilayers.
pH directly regulates epidermal permeability barrier homeostasis, and stratum corneum integrity/cohesion.
- J. Hachem, D. Crumrine, J. Fluhr, B. Brown, K. Feingold, P. Elias
- BiologyJournal of Investigative Dermatology
- 1 August 2003
It is demonstrated unequivocally that stratum corneum neutralization alone provokes stratumCorneum functional abnormalities, including aberrant permeability barrier homeostasis and decreased stratum Corneum integrity/cohesion, as well as the mechanisms responsible for these abnormalities.
Abnormal skin barrier in the etiopathogenesis of atopic dermatitis
Emerging evidence that the inflammation in AD results from inherited and acquired insults to the barrier is reviewed, as well as the therapeutic implications of this new paradigm.