Degradation of Fibronectin and Vitronectin and Vitronectin in Chronic Wound Fluid: Analysis by Cell Blotting, Immunoblotting, and Cell Adhesion Assays

Grinnell, Frederick; Ho, Cheryl; Wysocki, Annette B.

doi:10.1111/1523-1747.ep12499839

Cited by 223 publications

(142 citation statements)

References 34 publications

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“…Sallenave et al 116) have recently shown that leueo been reported that leucocyte elastase is responsible for extensive fibronectin degradation in burn wounds [9], Fur-cyte elastase is itself capable of inducing SKALP gene exthermore, in wound fluid from chronic leg ulcers fibro-pression in pneumocyte cell lines. However, we were itnnectin is almost completely degraded [10]. Since fibro-able to induce SKALP expression in nectin plays an important role in adhesion and migration of atinocytes under these conditions (Molhuizen et al, unepidermal cells [8 ], degradation of fibronectin and other published observation).…”

Section: Discussionmentioning

confidence: 79%

Expression of SKALP/elafin during wound healing in human skin

et al. 1996

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Skin-derived antileukoproteinase (SKALP), Key words SKALP • Wound healing • also known as elafin, is a proteinase inhibitor with Antileukoproteinase • Elastase specificity for polymorphonuclear leucocyte (PMN)-derived elastase and proteinase-3. SKALP is absent in normal human epidermis, but is strongly induced in Introduction inflammatory dermatoses such as psoriasis. SKALP is putatively involved in the regulation of cutaneous in-Proteinase activity is regulated systemically by numerous flammation by inhibiting PMN derived proteinases. plasma-derived inhibitors, such as a!-proteinase inhibitor The aim of this study was to investigate SKALP ex-and a 2-macroglobulin. However, in normal human epipression and PMN infiltration during wound healing dermis only low levels of antiproteinase activity directed in human skin. This was examined in healing exci-against the major polymorphonuclear leucocyte (PMN)-sional wounds in normal skin and in impaired healing derived proteinases (e.g. elastase, proteinase-3 and cathepin various types of chronic venous ulcers. Tissues were sin G) can be detected. Antiproteinase activity is upreguanalysed using immunohistocliemistry and Northern lated in inflammatory skin diseases such as psoriasis [5, blot analysis. Healing of excisional wounds was stud-18-20] and epidermal tumours [2]. In previous studies we ied from day 0 to day 14. An influx of PMN was seen and others have characterized this antiproteinase activity rapidly after wounding and was maximal between day and found it to be an inducible inhibitor of elastase and 2 and 4 and then subsided. SKALP was induced within proteinase 3 [23]. This inhibitor has been named skin-de-48 h and was expressed in the suprabasal keratino-rived antileukoproteinase (SKALP) [18], also known as cytes of the wound edge and the migrating epidermal elafin [23,24] or elastase-specific inhibitor (ESI) [15 |. sheet. SKALP expression was maximal on day 4 and Cloning of the SKALP cDNA and gene has revealed that was downregulated at the time of complete reepithe-the molecule contains several N-terminal transglutamilialization (7-14 days). In venous ulcers, PMN were nase substrate motifs, in addition to the antiproteinase doabundant in the wound bed and scarce under the main that was already known [11,12,14]. SKALP is a sewound edge. SKALP was strongly expressed in the creted molecule, and we have recently demonstrated its keratinocytes of the wound edge in all types of ulcers presence in urine and plasma of psoriatic patients [1,4]. studied. In the wound bed, SKALP was not detectable. Our results suggest that S SKALP may be involved in the regulation of euta-P plays a role in the neous animation by inhibiting PMN-derived o acute, inflammatory phase of wound healing. From teinases. However, no direct evidence for its function in the kinetics and topology of SKALP expression we vivo is available at present. Previous investigations have surmise that it negatively regulates PMN infiltration.

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Section: Discussionmentioning

confidence: 79%

Expression of SKALP/elafin during wound healing in human skin

et al. 1996

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“…In general, the possibility that the growth factor environment might change to facilitate migration or contraction has not be considered. Although the wound environment is rich in growth factors released from platelets, it also contains locally secreted factors including proteolytic enzymes [78][79][80]. Perhaps the highly proteolytic chronic wound environment becomes pro-contractile and unable to support fibroblast migration because of the destruction of PDGF [81], which might help explain the ability of recombinant PDGF (Regranex) to stimulate repair of chronic human wounds.…”

Section: Discussionmentioning

confidence: 99%

Fibroblast mechanics in 3D collagen matrices☆

Rhee

Grinnell²

2007

Advanced Drug Delivery Reviews

167

115

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Connective tissues provide mechanical support and frameworks for the other tissues of the body. Type 1 collagen is the major protein component of ordinary connective tissue, and fibroblasts are the cell type primarily responsible for its biosynthesis and remodeling. Research on fibroblasts interacting with collagen matrices explores all four quadrants of cell mechanics: pro-migratory vs. pro-contractile growth factor environments on one axis; high tension vs. low tension cell-matrix interactions on the other. The dendritic fibroblast -probably equivalent to the resting tissue fibroblast -can be observed only in the low tension quadrant and generally has not been appreciated from research on cells incubated with planar culture surfaces. Fibroblasts in the low tension quadrant require microtubules for formation of dendritic extensions, whereas fibroblasts in the high tension quadrant require microtubules for polarization but not for spreading. Ruffling of dendritic extensions rather than their overall protrusion or retraction provides the mechanism for remodeling of floating collagen matrices, and floating matrix remodeling likely reflects a model of tissue mechanical homeostasis.

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“…139,159,160 Moreover, fibronectin fragments (generated by fibronectin degradation) have been shown to modulate levels of MMPs and TIMPs in some models, 139,161 and have been reported to occur in chronic wound fluids. [162][163][164] As bidirectional signaling receptors that regulate both keratinocyte-mediated changes to the wound microenvironment, and keratinocyte responses to those microenvironmental changes, integrins are attractive targets for therapeutic strategies to promote wound healing or to treat chronic wounds. The general concept of therapeutically targeting integrin function is already well established.…”

Section: Future Directions Exploiting Integrins As Therapeutic Targetmentioning

confidence: 99%