Stromelysin-2 is upregulated during normal wound repair and is induced by cytokines

Stromelysin-2 is a matrix metalloproteinase that degrades in vitro several protein components relevant to wound repair such as collagens III and IV, g elatin, nidogen, laminin-1, proteoglycans, and elastin. Furthermore, it can activate other matrix metalloproteinases, such as collagenase-1 (matrix me talloproteinase-1) and collagenase-2 (matrix metalloproteinase-8), as well as 92 kDa gelatinase. The aim of this study was to determine in a large var iety of wounds (normally healing dermal and mucosal wounds, suction blister s, ex vivo cultures, diabetic, decubitus, rheumatic, and venous ulcers) and keratinocyte cultures, which factors contribute to stromelysin-2 expressio n and how it is induced in relation to other matrix metalloproteinases. Our results show that stromelysin-2 mRNA and protein are upregulated later (at 3 d) than matrix metalloproteinase-1 in normally healing wounds and ex viv o explants, in which stromelysin-2 is invariably expressed by keratinocytes migrating over dermal matrix. The number of keratinocytes expressing strom elysin-2 was greatest in chronic inflamed diabetic and venous ulcers compar ed with rheumatoid and decubitus ulcers, six of which had no signal. In ker atinocyte cultures, tumor necrosis factor-alpha, epidermal growth factor, a nd transforming growth factor-beta1 induced stromelysin-2 expression as mea sured by quantitative reverse transcriptase-polymerase chain reaction, wher eas different matrices did not upregulate the mRNA. Immunostaining demonstr ated stromal transforming growth factor-beta1 in contact with the stromelys in-2-positive keratinocytes. Our results suggest that stromelysin-2 express ion is important for the normal repair process and is upregulated by cytoki nes rather than cell-matrix interactions. Stromelysin-2 is most likely to p articipate in the remodeling of the newly formed basement membrane, and is not overexpressed in retarded wound healing.