Disorders of the cutaneous basement membrane zone--the paradigm of epidermolysis bullosa

Abstract

The cutaneous basement membrane zone (BMZ) is a highly specialized functional complex that provides the skin with structural adhesion and resistance to shearing forces. Its regulatory functions include control of epithelial-mesenchymal interactions under physiological and pathological conditions. Mutations in genes encoding components of the BMZ are associated with inherited skin disorders of the epidermolysis bullosa (EB) group, characterized by skin fragility, mechanically induced blisters and erosions of the skin and mucous membranes. Although most disease-associated genes are known, the genetic basis of new EB subtypes linked to mutations in genes for focal adhesion proteins was uncovered only recently. The molecular mechanisms leading to blistering, abnormal wound healing, predisposition to skin cancer, and other complications in EB have been elucidated using animal models and disease proteomics. The rapid progress in understanding the molecular basis of EB has enabled the development of strategies for biologically valid causal therapies.

Keywords: Adhesion; Blister; Cell–matrix adhesion; Dermal–epidermal junction; Kindler syndrome; Skin fragility.