Cathepsin D, but not cathepsin E, degrades desmosomes during epidermal desquamation.

Background: We previously reported that an ambient aspartic proteinase is crucial to desquamation of the stratum corneum at pH 5. Identification of this aspartic proteinase by using enzyme inhibitors suggested it to be cathepsin D, although we could not exclude cathepsin E.

Objectives: To determine the identity of this aspartic proteinase and its distribution within the stratum corneum.

Zinc-alpha(2)-glycoprotein hinders cell proliferation and reduces cdc2 expression.

Zinc-alpha(2)-glycoprotein (Znalpha(2)gp) is widely distributed in body fluids and epithelia. Its expression in stratified epithelia increases with differentiation. We previously showed that Zn alpha(2)gp has ribonuclease activity, and that squamous tumor cells grown on a matrix of Znalpha(2)gp were growth-inhibited.

Response of keratinocytes from normal and psoriatic epidermis to interferon-gamma differs in the expression of zinc-alpha(2)-glycoprotein and cathepsin D.

Psoriasis is a T cell-mediated inflammatory disease characterized by hyperproliferation and by aberrant differentiation. We found cathepsin D and zinc-alpha(2)-glycoprotein, two catalytic enzymes associated with apoptosis and desquamation, to be present in the stratum corneum of the normal epidermis but absent from the psoriatic plaque. Psoriasis is characterized by an altered response to interferon-gamma (IFN-gamma), including the induction of apoptosis in normal but not in psoriatic keratinocytes, often with opposite effects on gene expression of suprabasal proteins.

Role of endogenous cathepsin D-like and chymotrypsin-like proteolysis in human epidermal desquamation.

Even though the skin surface is acidic (about pH 5), most in vitro studies on desquamation have been performed at alkaline pH. We demonstrate that the standard in vitro model system, which achieves squame shedding upon incubation of plantar stratum corneum for 1 day in an alkaline buffer that must include a chelating agent, can be extended to a more realistic model in which the incubation is for 4 days, at varying pHs from 5 to 8, without exogenous chelators. Desmoglein I from stratum corneum was degraded by the squames shed at pH 5 as well as at pH 8.

Characterization of zinc-alpha(2)-glycoprotein as a cell adhesion molecule that inhibits the proliferation of an oral tumor cell line.

Zn-alpha(2)-glycoprotein (Znalpha(2)gp) is a soluble protein widely distributed in body fluids and glandular epithelia. We have found it to be expressed in stratified epithelia as well. Znalpha(2)gp is clinically correlated with differentiation in various epithelial tumors, including oral and epidermal tumors.