Differential expression patterns of proteins involved in epidermal proliferation and differentiation in canine atopic dermatitis

Abstract

The pathological alterations in skin keratinocyte proliferation and differentiation in canine atopic dermatitis (CAD) were investigated in 20 small breed dogs with CAD (10 of which displayed lesional CAD skin and 10 nonlesional CAD skin) and 11 healthy control animals. Biopsy of lesional CAD skin showed orthokeratotic hyperkeratosis. Immunohistochemistry (IHC) of Ki-67, a cellular marker for proliferation, showed a higher epidermal cell proliferation rate in the CAD dogs (p < 0.05) which positively correlated with Canine Atopic Dermatitis Extent and Severity Index, CADESI-03 (p < 0.01). IHC labeling indicated reduced expression of cornified envelope proteins, involucrin (IVL) and filaggrin (FLG) in both lesional and non-lesional skin (p < 0.05). In contrast, expression of lympho-epithelial Kazal-type inhibitor (LEKTI), which has been reported to inhibit proteases that cleave proFLG into FLG, was increased in lesional skin compared to the normal controls (p < 0.05). The IHC results showed a positive correlation between CADESI-03 and LEKTI expression and a negative correlation between CADESI-03 and IVL expression. In conclusion, the present study demonstrates that epidermal hyperkeratosis in CAD is related to disturbance of both epidermal proliferation and cornified envelope differentiation. This is the first report of a correlation of LEKTI with CAD.