Collagen VII plays a dual role in wound healing.

[dystrophic epidermolysis bullosa]

Although a host of intracellular signals is known to contribute to wound healing , the role of the cell microenvironment in tissue repair remains elusive . Here we employed 2 different mouse models of genetic skin fragility to assess the role of the basement membrane protein collagen VII (COL 7 A 1 ) in wound healing . COL 7 A 1 secures the attachment of the epidermis to the dermis , and its mutations cause a human skin fragility disorder coined recessive dystrophic epidermolysis bullosa (RDEB ) that is associated with a constant wound burden . We show that COL 7 A 1 is instrumental for skin wound closure by 2 interconnected mechanisms . First , COL 7 A 1 was required for re -epithelialization through organization of laminin-332 at the dermal-epidermal junction . Its loss perturbs laminin-332 organization during wound healing , which in turn abrogates strictly polarized expression of integrin Î±6 Î² 4 in basal keratinocytes and negatively impacts the laminin-332 /integrin Î±6 Î² 4 signaling axis guiding keratinocyte migration . Second , COL 7 A 1 supported dermal fibroblast migration and regulates their cytokine production in the granulation tissue . These findings , which were validated in human wounds , identify COL 7 A 1 as a critical player in physiological wound healing in humans and mice and may facilitate development of therapeutic strategies not only for RDEB , but also for other chronic wounds .

Diseases
Validation

Diseases presenting "strictly polarized expression" symptom

dystrophic epidermolysis bullosa

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