Reduced stability and bi-allelic, coequal expression of profilaggrin mRNA in keratinocytes cultured from subjects with Ichthyosis vulgaris

Nirunsuksiri, Wilas; Fleckman, P

doi:10.1016/s0923-1811(98)83115-0

Cited by 10 publications

(21 citation statements)

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“…Perhaps the best evidence that these amino acids do play a role in normal epidermal flexibility and desquamation is the human skin disorder ichthyosis vulgaris (IV). This disorder is characterized phenotypically by dry, flaky skin and biochemically by reduced or absent profilaggrin expression (Sybert et al, 1985;Nirunsuksiri et al, 1995Nirunsuksiri et al, , 1998. The defect in IV appears to be specific to profilaggrin, since other markers of epidermal differentiation such as keratin 1 or loricrin are expressed normally (Nirunsuksiri et al, 1995).…”

Section: (B) Skin Disorders Associated With Keratin Mutationsmentioning

confidence: 99%

Epithelial Structural Proteins of the Skin and Oral Cavity: Function in Health and Disease

Presland

Dale

2000

Critical Reviews in Oral Biology & Medicine

349

328

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Epithelial tissues function to protect the organism from physical, chemical, and microbial damage and are essential for survival. To perform this role, epithelial keratinocytes undergo a well-defined differentiation program that results in the expression of structural proteins which maintain the integrity of epithelial tissues and function as a protective barrier. This review focuses on structural proteins of the epidermis and oral mucosa. Keratin proteins comprise the predominant cytoskeletal component of these epithelia. Keratin filaments are attached to the plasma membrane via desmosomes, and together these structural components form a threedimensional array within the cytoplasm of epithelial cells and tissues. Desmosomes contain two types of transmembrane proteins, the desmogleins and desmocollins, that are members of the cadherin family. The desmosomal cadherins are linked to the keratin cytoskeleton via several cytoplasmic plaque proteins, including desmoplakin and plakoglobin (-y-catenin). Epidermal and oral keratinocytes express additional differentiation markers, including filaggrin and trichohyalin, that associate with the keratin cytoskeleton during terminal differentiation, and proteins such as loricrin, small proline-rich proteins, and involucrin, that are cross-linked into the cornified envelope by transglutaminase enzymes. The importance of these cellular structures is highlighted by the large numbers of genetic and acquired (autoimmune) human disorders that involve mutations in, or autoantibodies to, keratins and desmosomal and cornified envelope proteins. While much progress has been made in the identification of the structural proteins and enzymes involved in epithelial differentiation, regulation of this process is less clear. Both calcium and retinoids influence epithelial differentiation by altering the transcription of target genes and by regulating activity of enzymes critical in epithelial differentiation, such as transglutaminases proteinases, and protein kinases. These studies have furthered our understanding of how epithelial tissue and cell integrity is maintained and provide a basis for the future treatment of skin and oral disorders by gene therapy and other novel therapeutics.

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Section: (B) Skin Disorders Associated With Keratin Mutationsmentioning

confidence: 99%

Epithelial Structural Proteins of the Skin and Oral Cavity: Function in Health and Disease

Presland

Dale

2000

Critical Reviews in Oral Biology & Medicine

349

328

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“…Decreased FLG expression results in a paucity of keratohyalin granules, which is a hallmark of ichthyosis vulgaris (IV), independent of body site and season of the year. [1][2][3][4] IV, the most prevalent disorder of cornification in humans, is characterized by the delayed, postnatal onset of generalized, fine scaling that spares the flexures, and is often associated with palmar hyperlinearity and atopic dermatitis (AD). [5][6][7] In IV and AD, both nonsense and frameshift mutations have been discovered in the gene encoding FLG, which localizes to the epidermal differentiation complex on chromosome 1q21.…”

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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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“…Loss of filaggrin expression has been observed in the epidermal keratinocytes of ichthyosis vulgaris (IV) patients (Sybert et al 1985;Nirunsuksiri et al 1998). However, the many repeats in its sequence hindered the sequencing of FLG, which encodes filaggrin.…”

Section: Assessment Of Epidermal Barrier Functionmentioning

confidence: 99%

Epidermal Barriers

Natsuga

2014

Cold Spring Harbor Perspectives in Medicine

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The epidermis functions as a physical barrier to the external environment and works to prevent loss of water from the skin. Numerous factors have been implicated in the formation of epidermal barriers, such as cornified envelopes, corneocytes, lipids, junctional proteins, proteases, protease inhibitors, antimicrobial peptides, and transcription factors. This review illustrates human diseases (ichthyoses) and animal models in which the epidermal barrier is disrupted or dysfunctional at steady state owing to ablation of one or more of the above factors. These diseases and animal models help us to understand the complicated mechanisms of epidermal barrier formation and give further insights on epidermal development.

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Reduced stability and bi-allelic, coequal expression of profilaggrin mRNA in keratinocytes cultured from subjects with Ichthyosis vulgaris

Cited by 10 publications

References 0 publications

Epithelial Structural Proteins of the Skin and Oral Cavity: Function in Health and Disease

Epithelial Structural Proteins of the Skin and Oral Cavity: Function in Health and Disease

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

Epidermal Barriers

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