BACKGROUND: Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) have important functions during skin development, repair and maintenance. @entity1476 and @entity1495 (gelatinase A and gelatinase B) are involved in regulating keratinocyte migration. OBJECTIVES: To analyse whether Apligraf, a bilayered tissue-engineered @entity1 skin equivalent (HSE), produces gelatinases and TIMPs and whether or not epidermal-dermal interactions regulate MMP activity. METHODS: The tissue distribution of @entity1476 , @entity1495 , @entity2843 , @entity1552 and fibronectin was analysed by immunohistochemistry. Secreted MMP activity was quantified by a fluorimetric assay and gelatin zymography was used to monitor gelatinases in tissue culture supernatants. RESULTS: Apligraf expressed @entity1476 and @entity1495 and contained immunohistochemically detectable amounts of @entity2843 and @entity1552 . The gelatinases were predominantly produced in the epidermis, whereas immunostaining of @entity2843 and @entity1552 was largely confined to the dermal component of the HSE. Fibronectin was expressed only in the dermis. Gelatin zymography demonstrated that intact Apligraf produced both @entity1476 and @entity1495 , the latter predominantly in its latent form. Separation of the dermis from the epidermis resulted in an enhanced production and activation of @entity1495 by the epidermal layer, and secretion of latent and active @entity1476 by the dermal layer. Moreover, the incubation media of the separated epidermis demonstrated significantly stronger MMP activity than did intact Apligraf or its dermal component. CONCLUSIONS: These observations provide evidence that epidermal-dermal interactions suppress epidermal gelatinase activity. In addition, coexpression of TIMPs and fibronectin in the Apligraf dermis suggests that the product has the potential to counteract the imbalance between matrix production and degradation in chronic wounds and thus may support wound re-epithelialization.

Epidermal-dermal interactions regulate gelatinase activity in Apligraf, a tissue-engineered XXXX skin equivalent.

@entity1 :: ('9606', 'Species') :: ['human'] @entity1552 :: ('7077', 'Gene') :: ['TIMP-2'] @entity1476 :: ('4313', 'Gene') :: ['MMP-2'] @entity2843 :: ('7076', 'Gene') :: ['TIMP-1'] @entity1495 :: ('4318', 'Gene') :: ['MMP-9']
@entity1 :: (9606,Species) :: ['human']
