Epidermal aspects of type VII collagen: Implications for dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita

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Epidermal aspects of type VII collagen: Implications for dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita (1)

In 28 different types of collagen family, type VII collagen (COL7) is a major component of anchoring fibrils, which extend from the basal lamina to the dermis in the epidermal basement membrane zone. COL7 has been implicated in two human disorders, namely dystrophic epider- molysis bullosa (DEB) and epidermolysis bullosa acquisita (EBA). DEB is categorized into two major subtypes, namely autosomal recessive DEB (RDEB) and autosomal dominant DEB (DDEB). EBA is an autoimmune subepidermal blistering disorder characterized by circulating autoantibodies to COL7. Experimental EBA models have revealed that attachment of autoantibodies to COL7 evokes inflammatory reactions that eventually lead to erythema and blister formation.

COL7 is a major component of anchoring fibrils in human skin and consists of a non-collagenous NC-1 domain, a triple helical collagenous domain and an NC-2 domain. The role of the NC-1 domain is to maintain the triple helix structure of COL7 in the cytoplasm, while the NC-2 domain of COL7 is removed through a proteolytic process in the ECM to stabilize the dimer assembly of COL7. The role of the NC-1 domain is to maintain the triple helix structure of COL7 in the cytoplasm, while the NC-2 domain of COL7 is removed through a proteolytic process in the ECM to stabilize the dimer assembly of COL7. In vitro cell culture experiments have demonstrated that COL7 is produced by both dermal fibroblasts and epidermal keratinocytes.

ECM and basement membrane zone proteins including a6 integrin, b1 integrin and COL17 create a niche for epidermal stem cell maintenance through mechanical support and/or stabilization of signaling molecules. In epidermal keratinocytes, TGF-b1/2 treatment increased COL7A1 mRNA levels.

1. M. Watanabe, K. Natsuga, S. Shinkuma, H. Shimizu, Epidermal aspects of type VII collagen: Implications for dystrophic epidermolysis bullosa and epidermolysis bullosa acquisita. J. Dermatol. 45, 515–521 (2018).

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