Matrix Metalloproteinases and the Ontogeny of Scarless Repair: The Other Side of the Wound Healing Balance

Peled, Ziv M.; Phelps, Eric D.; Updike, Dawn L.; Krummel, Thomas M.; Howard, Eric W.; Longaker, Michael T.

doi:10.1097/00006534-200209010-00013

Cited by 39 publications

(6 citation statements)

References 45 publications

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“…In addition to differences in the composition of the ECM, there are notable differences in the expression of matrix metalloproteinases involved in the degradation of the ECM. Fetal skin wounds have been shown to have a higher matrix metalloproteinase to tissue inhibitor of metalloproteinase ratio [ 16 , 17 ]. Similar to fetal wounds, Acomys wounds have significantly higher levels of expression of Mmp2 and Mmp9 , and lower levels of expression of Timp1 in day 3 and 5 wounds compared to Mus .…”

Section: Discussionmentioning

confidence: 99%

A Comparative Analysis of Gene Expression Profiles during Skin Regeneration in Mus and Acomys

et al. 2015

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The African spiny mouse (Acomys spp.) can heal full thickness excisional skin wounds in a scar-free manner with regeneration of all dermal components including hair and associated structures. Comparing Acomys scar-free healing from Mus scarring identifies gene expression differences that discriminate these processes. We have performed an extensive comparison of gene expression profiles in response to 8mm full-thickness excisional wounds at days 3, 5, 7 and 14 post-wounding between Acomys and Mus to characterize differences in wound healing, and identify mechanisms involved in scar-free healing. We also identify similarities with scar-free healing observed in fetal wounds. While wounding in Mus elicits a strong inflammatory response, wounding in Acomys produces a moderated immune response and little to no increase in expression for most cytokines and chemokines assayed. We also identified differences in the ECM profiles of the Acomys wounds, which appear to have a collagen profile more similar to fetal wounds, with larger increases in expression of collagen types III and V. In contrast, Mus wounds have very high levels of collagen XII. This data suggests that an overall lack of induction of cytokines and chemokines, coupled with an ECM profile more similar to fetal wounds, may underlie scar-free wound healing in Acomys skin. These data identify candidate genes for further testing in order to elucidate the causal mechanisms of scar-free healing.

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Section: Discussionmentioning

confidence: 99%

A Comparative Analysis of Gene Expression Profiles during Skin Regeneration in Mus and Acomys

et al. 2015

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“…Although most of the studies indicate that dermal fibroblasts do not express MMP-9, it has been shown that TGF β1 and tumor necrosis factor α (TNFα) stimulate MMP-9 expression in human dermal fibroblasts (Han et al, 2001; Kobayashi et al, 2003). Moreover, Peled et al showed differences in MMP-2 and MMP-9 expression between fetal fibroblasts from scar-free and scar-forming stages of gestation (Peled et al, 2002). Similarly, abundant MMP-13 expression was detected in fibroblasts from gingival wounds and fetal skin wounds which heal with minimal scarring (Ravanti et al, 1999; Ravanti et al, 2001) suggesting a role for MMP-13 in scarless repair (Toriseva and Kahari, 2009).…”

Section: Discussionmentioning

confidence: 99%

Scarless skin wound healing in FOXN1 deficient (nude) mice is associated with distinctive matrix metalloproteinase expression

Gawrońska‐Kozak

2011

Matrix Biology

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Similar to mammalian fetuses FOXN1 deficient (nude) mice are able to restore the structure and integrity of injured skin in a scarless healing process by mechanisms independent of the genetic background. Matrix metalloproteinases (MMPs) are required for regular skin wound healing and the distinctive pattern of their expression has been implicated to promote scarless healing. In this study, we analyzed the temporal and spatial expression patterns of these molecules during the incisional skin wounds in adult nude mice. Macroscopic and histological analyses of skin wounds revealed an accelerated wound healing process, minimal granulation tissue formation and markedly diminished scarring in nude mice. Quantitative RT-PCR (Mmp-2,-3,-8,-9,-10,-12,-13,-14 and Timp-1, -2, -3), Western blots (MMP-13) and gelatin zymography (MMP-9) revealed that MMP-9 and MMP-13 showed a unique, bimodal pattern of up-regulation during the early and late phases of wound healing in nude mice. Immunohistochemically MMP-9 and MMP-13 were generally detected in epidermis during the early phase and in dermis during the late (remodeling) phase. Consistent with these in vivo observations, dermal fibroblasts cultured from nude mice expressed higher levels of type I and III collagen, MMP-9 and MMP-13 mRNA levels and higher MMP enzyme activity than wild type controls. Collectively, these finding suggest that the bimodal pattern of MMP-9 and MMP-13 expression during skin repair process in nude mice could be a major component of their ability for scarless healing.

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“…98 Increased MMP expression in scars has been observed at least 1.5 years postwounding 90 but their precise roles in excessive scarring or scarless wound healing need further clarification. 99 In situ hybridization methods have proved useful in identifying sites of mRNA coding for MMPs and mechanisms of up-regulation. 91,100 Elevated levels of MMP-1 mRNA were demonstrated mainly in 12-24-hour human wound fibroblasts 100 and in migrating epidermal tongues as part of the acute phase in wound healing.…”

Section: Mmpsmentioning

confidence: 99%

Zinc in wound healing: Theoretical, experimental, and clinical aspects

Lansdown

Mirastschijski

Stubbs

et al. 2007

Wound Repair Regeneration

554

404

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Zinc is an essential trace element in the human body and its importance in health and disease is appreciated. It serves as a cofactor in numerous transcription factors and enzyme systems including zinc-dependent matrix metalloproteinases that augment autodebridement and keratinocyte migration during wound repair. Zinc confers resistance to epithelial apoptosis through cytoprotection against reactive oxygen species and bacterial toxins possibly through antioxidant activity of the cysteine-rich metallothioneins. Zinc deficiency of hereditary or dietary cause can lead to pathological changes and delayed wound healing. Oral zinc supplementation may be beneficial in treating zinc-deficient leg ulcer patients, but its therapeutic place in surgical patients needs further clarification. Topical administration of zinc appears to be superior to oral therapy due to its action in reducing superinfections and necrotic material via enhanced local defense systems and collagenolytic activity, and the sustained release of zinc ions that stimulates epithelialization of wounds in normozincemic individuals. Zinc oxide in paste bandages (Unna boot) protects and soothes inflamed peri-ulcer skin. Zinc is transported through the skin from these formulations, although the systemic effects seem insignificant. We present here the first comprehensive account of zinc in wound management in relation to current concepts of wound bed preparation and the wound-healing cascade. This review article suggests that topical zinc therapy is underappreciated even though clinical evidence emphasizes its importance in autodebridement, anti-infective action, and promotion of epithelialization.

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Matrix Metalloproteinases and the Ontogeny of Scarless Repair: The Other Side of the Wound Healing Balance

Cited by 39 publications

References 45 publications

A Comparative Analysis of Gene Expression Profiles during Skin Regeneration in Mus and Acomys

A Comparative Analysis of Gene Expression Profiles during Skin Regeneration in Mus and Acomys

Scarless skin wound healing in FOXN1 deficient (nude) mice is associated with distinctive matrix metalloproteinase expression

Zinc in wound healing: Theoretical, experimental, and clinical aspects

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