Stromelysin-2 is Upregulated During Normal Wound Repair and is Induced by Cytokines

Abstract

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.

Expression of matrix metalloproteinase-10 in human bladder transitional cell carcinoma

“…Recently, a close relationship has been suggested between expression of MMP-10 and laminin-5, an ECM protein central to cell migration and cell adhesion 30,31 . Interestingly, enhanced loss from the basement membrane of laminin-5 occurs early in urothelial cell carcinoma, is associated with development of an invasive tumor phenotype and reorganization of the ECM at the invasive tumor front 31 .…”

Matrix metalloproteinase‐19 is expressed by proliferating epithelium but disappears with neoplastic dedifferentiation

“…The study was approved by the Ethics Committees of the Departments of Dermatology and Plastic Surgery, Helsinki University Central Hospital. Tissue samples included normal skin (n ϭ 4); lichenoid acanthotic dermatitis (n ϭ 3); 6 normally healing wounds; 14 venous, decubitus, diabetic, rheumatoid and clinically well-granulating chronic ulcers (n ϭ 20); premalignant tumors such as Bowen's disease (n ϭ 4) and solar keratosis, [malignant epidermal tumors, i.e., BCCs (n ϭ 16; sclerosing subtype n ϭ 7, nodular subtype n ϭ 9) and SCCs, grades I (n ϭ 2), II (n ϭ 14), III (n ϭ 6) and IV (n ϭ 2)]. Formalin-fixed, paraffin-embedded archival specimens were obtained from the Department of Dermatopathology, Skin and Allergy Hospital, University of Helsinki.…”

Androgens influence expression of matrix proteins and proteolytic factors during cutaneous wound healing

“…8 Of particular current interest are the varied roles of MMPs during skin repair. 9 Collagenase-1 (MMP-1) 10 and stromelysin-2 (MMP-10), 11 induced in basal epidermal cells at the wound edge, facilitate keratinocyte migration and/or remodeling of the newly restored basement membrane. Gelatinase A (MMP-2) also is expressed by the epidermis following injury and, along with gelatinase B (MMP-9), 12 by infiltrating macrophages.…”