Membrane Structures in Normal and Essential Fatty Acid-Deficient Stratum Corneum: Characterization by Ruthenium Tetroxide Staining and X-Ray Diffraction

Hou, Sui Yuen E.; Mitra, Alok K.; White, Stephen H.; Menon, Gopinathan K.; Ghadially, Ruby; Elias, Peter M.

doi:10.1111/1523-1747.ep12461361

Cited by 289 publications

(195 citation statements)

References 30 publications

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“…Ultrathin sections were stained with uranyl acetate and lead citrate. For visualization of membrane structures in the cornified layer, ruthenium tetroxide postfixation was used as described (33). Dye Penetration Assay.…”

Section: Methodsmentioning

confidence: 99%

Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1

Magnúsdóttir

Kalachikov

Mizukoshi

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

141

158

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The cornified layer is a compacted lattice of lipid-embedded corneocytes that provides an organism's barrier to the external environment. Cornification is the final differentiative step for epidermal keratinocytes and involves dramatic cell condensation before death. Using conditional gene deletion in mice, we identified the transcriptional repressor Blimp-1 (B lymphocyte-induced maturation protein-1) as an important regulator of keratinocyte transition from the granular to the cornified layer. More than 250 genes are misregulated in conditional knockout epidermis, including those encoding transcription factors, signal transduction components, proteinases, and enzymes involved in lipid metabolism. Steady-state mRNA and ChIP analyses of a subset of these genes provide evidence that nfat5, fos, prdm1, and dusp16 are novel direct targets of Blimp-1. Identifying nfat5 as a target of Blimp-1 repression indicates that cornification involves suppression of normal osmotic regulation in granular cells. Consistently, conditional knockout mice have delayed barrier formation as embryos, enlarged granular layer cells and corneocytes, and a morphologically abnormal cornified layer. These studies provide insight into cornification, identifying transcriptional regulatory circuitry and indicating the importance of blocking osmotic homeostasis.cornification ͉ epidermis ͉ prdm1 ͉ transcription factors ͉ nfat5

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Section: Methodsmentioning

confidence: 99%

Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1

Magnúsdóttir

Kalachikov

Mizukoshi

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

141

158

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“…Premature rat pups were obtained by cesarean section using isofluorane or halothane anesthesia at 18,19,20,21, and 22 (term) d EGA. Neonates were patted dry immediately after delivery and floated with their placental connections intact on a raft in a 36°C water bath.…”

Section: Methodsmentioning

confidence: 99%

“…Samples were then washed in 0.1 M sodium cacodylate buffer and 5% sucrose for 24 h at 4°C and postfixed in either 0.2% ruthenium tetroxide or 2% reduced osmium tetroxide (20). Tissue samples were dehydrated in a graded ethanol series and subsequently embedded in an epon-epoxy mixture (46).…”

Section: Methodsmentioning

confidence: 99%

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Ontogeny of the Epidermal Barrier to Water Loss in the Rat: Correlation of Function with Stratum Corneum Structure and Lipid Content

et al. 1992

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ABSTRACT. The mammalian epidermal permeability barrier is provided by highly hydrophobic lipids forming multiple membrane bilayers within the extracellular domains of the outer, cornified cell layers. To characterize the critical events associated with barrier maturation, we correlated the emergence of a competent barrier to transepidermal water loss with development of the lamellar body secretory system, the organization of stratum corneum membrane bilayers, and the lipid composition of these membranes in the perinatal rat. The primary function of mammalian epidermis during terrestrial life is the generation and maintenance of a competent bamer

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“…56 Skin samples, derived from punch biopsies, were minced to Ͻ0.5 mm 3 fragments, rinsed three times in 0.1 mol/L cacodylate buffer, and pre-fixed in half-strength Karnovsky's fixative, followed by postfixation in reduced 1% osmium tetroxide (OsO 4 ) containing 1.5% ferrocyanide or in 0.2% ruthenium tetroxide (RuO 4 ). [57][58][59] Selected samples were immersed for 2 hours in absolute pyridine for visualization of the cornified lipid envelope, followed by OsO 4 postfixation, as described previously. 54,60 The combination of osmium (OsO 4 ) and ruthenium tetroxide (RuO 4 ) postfixation protocols with pyridine pretreatment allowed us to assess the CE scaffold in relation to the extracellular lamellar bilayer system, as described previously.…”

Section: Electron Microscopymentioning

confidence: 99%

Filaggrin Genotype in Ichthyosis Vulgaris Predicts Abnormalities in Epidermal Structure and Function

Gruber

Elias

Crumrine

et al. 2011

The American Journal of Pathology

219

238

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Although it is widely accepted that filaggrin (FLG) deficiency contributes to an abnormal barrier function in ichthyosis vulgaris and atopic dermatitis, the pathomechanism of how FLG deficiency provokes a barrier abnormality in humans is unknown. We report here that the presence of FLG mutations in Caucasians predicts dose-dependent alterations in epidermal permeability barrier function. Although FLG is an intracellular protein, the barrier abnormality occurred solely via a paracellular route in affected stratum corneum. Abnormal barrier function correlated with alterations in keratin filament organization (perinuclear retraction), impaired loading of lamellar body contents, followed by nonuniform extracellular distribution of secreted organelle contents, and abnormalities in lamellar bilayer architecture. In addition, we observed reductions in corneodesmosome density and tight junction protein expression. Thus, FLG deficiency provokes alterations in keratinocyte architecture that influence epidermal functions localizing to the extracellular matrix.These results clarify how FLG mutations impair epidermal permeability barrier function.

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Membrane Structures in Normal and Essential Fatty Acid-Deficient Stratum Corneum: Characterization by Ruthenium Tetroxide Staining and X-Ray Diffraction

Cited by 289 publications

References 30 publications

Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1

Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1

Ontogeny of the Epidermal Barrier to Water Loss in the Rat: Correlation of Function with Stratum Corneum Structure and Lipid Content

Filaggrin Genotype in Ichthyosis Vulgaris Predicts Abnormalities in Epidermal Structure and Function

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