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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Filaggrin expression in epidermolytic ichthyosis (epidermolytic hyperkeratosis).

To evaluate the role of filaggrin in keratin filament aggregation in epidermolytic ichthyosis (epidermolytic hyperkeratosis, EH), we studied EH skin by light and electron microscopic immunohistochemistry, and biochemical analysis using sodium dodecylsulphate-polyacrylamide gel electrophoresis and immunoblotting. Immunohistochemical staining showed an increased number of filaggrin-immunoreactive cell layers, but the reaction was still confined to the mid- and upper epidermal layers, whereas an abnormal granular pattern of staining for K10 began in the lower suprabasal cell layers. This suggests that the aggregation of keratin filaments precedes, and occurs independently of, profilaggrin synthesis during epidermal differentiation. Although keratohyalin granules were frequently associated with clumped filaments, immunoelectron microscopy showed that K10 labelling was confined to keratin filaments (including clumped filaments), and that antifilaggrin antibodies stained only keratohyalin granules, at least in the living cells. Certain keratin aggregates in the cornified cells were still devoid of filaggrin staining. However, in some cells which appeared partially cornified, filaggrin immunoreactivity occurred over the aggregated keratin filaments. Immunoblotting showed a clear increase of filaggrin/profilaggrin expression, without evidence for a qualitative abnormality. It seems unlikely, therefore, that filaggrin is primarily involved in the keratin filament clumping in EH, but that in some EH cases it interacts with keratins in a defective manner, possibly due to premature cell death and profilaggrin processing and/or altered keratin filament structure involving the interaction points of keratin with filaggrin.[1]


  1. Filaggrin expression in epidermolytic ichthyosis (epidermolytic hyperkeratosis). Ishida-Yamamoto, A., Eady, R.A., Underwood, R.A., Dale, B.A., Holbrook, K.A. Br. J. Dermatol. (1994) [Pubmed]
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