Abstract |
The ability to regulate wound contraction is critical for wound healing as well as for pathological contractures. Matrix metalloproteinases ( MMPs) have been demonstrated to be obligatory for normal wound healing. This study examined the effect that the broad-spectrum MMP inhibitor BB-94 has when applied topically to full-thickness skin excisional wounds in rats and its ability to inhibit the promotion of myofibroblast formation and function by the latent transforming-growth factor-beta1 (TGF-beta1). BB-94 delayed wound contraction, as well as all other associated aspects of wound healing examined, including myofibroblast formation, stromal cell proliferation, blood vessel formation, and epithelial wound coverage. Interestingly, BB-94 dramatically increased the level of latent and active MMP-9. The increased levels of active MMP-9 may eventually overcome the ability of BB-94 to inhibit this MMP and may explain why wound contraction and other associated events of wound healing were only delayed and not completely inhibited. BB-94 was also found to inhibit the ability of latent TGF-beta1 to promote the formation and function of myofibroblasts. These results suggest that BB-94 could delay wound closure through a twofold mechanism; by blocking keratinocyte migration and thereby blocking the necessary keratinocyte-fibroblast interactions needed for myofibroblast formation and by inhibiting the activation of latent TGF-beta1.
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Authors | Ursula Mirastschijski, Reinhild Schnabel, Juliane Claes, Wolfgang Schneider, Magnus S Agren, Carol Haaksma, James J Tomasek |
Journal | Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
(Wound Repair Regen)
2010 Mar-Apr
Vol. 18
Issue 2
Pg. 223-34
ISSN: 1524-475X [Electronic] United States |
PMID | 20409148
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Protease Inhibitors
- Thiophenes
- Transforming Growth Factor beta1
- Phenylalanine
- batimastat
- Matrix Metalloproteinase 9
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Topics |
- Animals
- Cell Proliferation
(drug effects)
- Fibroblasts
(drug effects)
- Matrix Metalloproteinase 9
(drug effects)
- Neovascularization, Physiologic
(drug effects)
- Phenylalanine
(analogs & derivatives, pharmacology)
- Protease Inhibitors
(pharmacology)
- Rats
- Skin
(cytology)
- Stromal Cells
(drug effects, metabolism)
- Thiophenes
(pharmacology)
- Transforming Growth Factor beta1
(antagonists & inhibitors)
- Wound Healing
(drug effects, physiology)
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