p38δ mitogen-activated protein kinase regulates the expression of tight junction protein ZO-1 in differentiating human epidermal keratinocytes.

Increasing evidence has recognized tight junctions (TJs) as the lower epidermal inside-out diffusion barrier located in granular cell layers of the epidermis. However, little is known about the regulation of TJ components in epidermis. p38 pathway is one of the mitogen-activated protein kinase pathways, which controls cell growth, differentiation, and apoptosis.

Hailey-Hailey disease and tight junctions: Claudins 1 and 4 are regulated by ATP2C1 gene encoding Ca(2+) /Mn(2+) ATPase SPCA1 in cultured keratinocytes.

Mutations in the ATP2C1 gene encoding Ca(2+) /Mn(2+) ATPase SPCA1 cause Hailey-Hailey disease (HHD, OMIM 16960). HHD is characterized by epidermal acantholysis. We attempted to model HHD using normal keratinocytes, in which the SPCA1 mRNA was down-regulated with the small inhibitory RNA (siRNA) method.

Desmosomes in developing human epidermis.

Desmosomes play important roles in the cell differentiation and morphogenesis of tissues. Studies on animal models have greatly increased our knowledge on epidermal development while reports on human developing skin are rare due to the difficult accessibility to the samples. Although the morphology of periderm cells and the process how the epidermis develops very much resemble each other, the timetable and the final outcome of a mature human epidermis markedly differ from those of murine skin.

Tight junctions in Hailey-Hailey and Darier's diseases.

Hailey-Hailey disease (HHD) and Darier's disease (DD) are caused by mutations in Ca(2+)-ATPases with the end result of desmosomal disruption and suprabasal acantholysis. Tight junctions (TJ) are located in the granular cell layer in normal skin and contribute to the epidermal barrier. Aberrations in the epidermal differentiation, such as in psoriasis, have been shown to lead to changes in the expression of TJ components.