Content » Vol 100, 100-year theme: Blistering skin disorders (Feb)


Collagen XVII Processing and Blistering Skin Diseases

Wataru Nishie
DOI: 10.2340/00015555-3399


Collagen XVII (COL17) is a hemidesmosomal transmembrane protein in the skin, which, in several autoimmune blistering skin diseases, may be targeted by autoantibodies. In addition, loss-of-function mutations in the COL17A1 gene induce a subtype of junctional epidermolysis bullosa. The extracellular domain of COL17 can be physiologically cleaved from the cell surface by ADAM family proteins in a process known as ectodomain shedding. COL17 ectodomain shedding is thought to be associated with the migration and proliferation of keratinocytes. Furthermore, the C-terminal cleavage of COL17 may be associated with basement membrane formation. COL17 can be targeted by various proteases, including MMP9, neutrophil elastase, plasmin and granzyme B, which may be associated with blister formation in pemphigoid diseases. Interestingly, cleavage of COL17 may induce neoepitopes on the proteolysed fragments, and such induction is associated with dynamic structural changes. This review summarizes the current understanding of cleavage of COL17, and how such cleavage relates to blistering skin diseases.


Collagen XVII (COL17, also known as BP180) is an important molecule, which maintains stable adhesion between the dermis and epidermis. Genetic and acquired dysfunctions of COL17 lead to blistering skin diseases. However, the expression of COL17 is tightly regulated, depending on various settings, including wound-healing, proliferation and differentiation. Dysregulation of COL17 processing may be associated with the development of blistering skin diseases; thus, it is important to understand the mechanism by which COL17 is processed and the diseases associated with such processing.

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