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, gelatin, nidogen, laminin-1, proteoglycans, and elastin. Furthermore, it can activate other matrix metalloproteinases, such as collagenase-1 (matrix metalloproteinase-1) and collagenase-2 (matrix metalloproteinase-8), as well as 92 kDa gelatinase. The aim of this study was to determine in a large variety of wounds (normally healing dermal and mucosal wounds, suction blisters, ex vivo cultures, diabetic, decubitus, rheumatic, and venous ulcers) and keratinocyte cultures, which factors contribute to stromelysin-2 expression 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 vivo explants, in which stromelysin-2 is invariably expressed by keratinocytes migrating over dermal matrix. The number of keratinocytes expressing stromelysin-2 was greatest in chronic inflamed diabetic and venous ulcers compared with rheumatoid and decubitus ulcers, six of which had no signal. In keratinocyte cultures, tumor necrosis factor-alpha, epidermal growth factor, and transforming growth factor-beta1 induced stromelysin-2 expression as measured by quantitative reverse transcriptase-polymerase chain reaction, whereas different matrices did not upregulate the mRNA. Immunostaining demonstrated stromal transforming growth factor-beta1 in contact with the stromelysin-2-positive keratinocytes. Our results suggest that stromelysin-2 expression is important for the normal repair process and is upregulated by cytokines rather than cell-matrix interactions. Stromelysin-2 is most likely to participate in the remodeling of the newly formed basement membrane, and is not overexpressed in retarded wound healing.
Rechardt
O
O
Departments of Dermatology, Helsinki University Central Hospital, Helsinki, Finland.
Elomaa
O
O
Vaalamo
M
M
Pääkkönen
K
K
Jahkola
T
T
Höök-Nikanne
J
J
Hembry
R M
RM
Häkkinen
L
L
Kere
J
J
Saarialho-Kere
U
U
D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002450:Cell Communication; D002465:Cell Movement; D016207:Cytokines / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology; D015603:Keratinocytes / Q000166:cytology; D053506:Matrix Metalloproteinase 10; D008666:Metalloendopeptidases / Q000235:genetics / Q000502:physiology*; D009504:Neutrophils / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D012883:Skin Ulcer / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects*; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D016207:Cytokines; D004815:Epidermal Growth Factor; D053506:Matrix Metalloproteinase 10; D008666:Metalloendopeptidases; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D000097794:Kalinin