In human skin, the 27-kd
heat shock protein (hsp27), a member of the small hsp family, is expressed mainly in the upper epidermal layers. Hsp27 functions as a
molecular chaperone and is involved in the regulation of cell growth and differentiation. According to experimental evidence, epidermal hsp27, through its chaperone function, might play a role in the assembly of
keratin filaments and the cornified cell envelope. This study was conducted to assess the expression pattern of hsp27 in a panel of different
ichthyoses. Twelve hereditary and acquired
skin diseases associated with an ichthyotic phenotype and 2 corresponding mouse models were investigated by immunohistochemistry on
formalin-fixed
paraffin-embedded tissue, using a
monoclonal antibody specific for hsp27. In
ichthyosis vulgaris,
lamellar ichthyosis,
Sjögren-Larsson syndrome,
Netherton syndrome, and acquired ichthyosiform skin condition, the pattern of hsp27 expression resembles healthy human skin. Hsp27 expression was reduced in
bullous ichthyosiform erythroderma and annular
epidermolytic ichthyosis, and absent in X-linked recessive
ichthyosis (1/3 patients) and congenital hemidysplasia with ichthyosiform
nevus and limb defects syndrome (1/1). In X-linked dominant chondrodysplasia, 3 small samples are completely negative and 2 larger samples show a pattern resembling random X inactivation. In the mouse models, tattered and bare patches, representing the murine analogues to X-linked dominant chondrodysplasia and congenital hemidysplasia with ichthyosiform
nevus and limb defects syndrome, expression of hsp25 (the murine homologue of hsp27) also showed lyonization, demonstrating a clear-cut link between hsp27 expression and underlying molecular pathology. Our results show that loss of hsp27 is a rare event in human epidermis that is associated with specific genetic defects. Among the cases described here, these defects are either in suprabasal
keratins or in
enzymes involved in
cholesterol biosynthesis. The expression and chaperone function of hsp27 might be modified by low/absent epidermal
cholesterol and aberrant substrates (ie,
keratins) resulting in
protein misfolding, dyskeratosis, and thus contribute to the ichthyotic phenotype.