Role of Degradative Enzymes in Wound Healing

Mignatti, Paolo; Welgus, Howard G.; Rifkin, Daniel B.

doi:10.1007/978-1-4615-1795-5_21

Cited by 13 publications

(6 citation statements)

References 193 publications

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“…The major substrate for PA is plasminogen. Plasminogen is present in both intravascular and extravascular sites including the extracellular matrix of endothelial cells (Mignatti et al, 1988). The active form of u-PA converts the proenzyme plasminogen to plasmin.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of action of angiostatic steroids: Suppression of plasminogen activator activity via stimulation of plasminogen activator inhibitor synthesis

Blei

Mignatti

et al. 1993

Journal Cellular Physiology

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132

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Recently, a novel class of angiostatic steroids which block angiogenesis in several systems has been described. Since the elaboration of proteases is believed to be an important component of angiogenesis, we tested whether these steroids blocked the fibrinolytic response of endothelial cells to the angiogenic protein, basic fibroblast growth factor [bFGF]). Cultured bovine aortic endothelial (BAE) cells were incubated with bFGF and/or medroxyprogesterone acetate (MPA), an angiostatic steroid which has been shown to inhibit vascularization, collagenolysis, and tumor growth. When bFGF (3 ng/ml) was added to confluent monolayers of BAE cells, plasminogen activator (PA) activity in the medium was increased threefold. In contrast, MPA at 10(-6) M, 10(-7) M, 10(-8) M, and 10(-9) M decreased PA levels in the medium by 83%, 83%, 75%, and 39%, respectively. The stimulation of PA levels in BAE cells by bFGF (3 ng/ml) was abrogated by the presence of 10(-6) M MPA. This decrease in PA activity was found to be mediated by a significant increase in plasminogen activator inhibitor type-1 (PAI-1) production. MPA, therefore, negated one of the important enzymatic activities associated with the angiogenic process. In contrast to the decreased levels of secreted PA in cultures exposed simultaneously to MPA and bFGF, cell-associated PA levels remained high, consistent with earlier observations indicating that PAI-1 does not inhibit cell-associated PA. Thus, angiostatic steroids may exert their inhibitory effects on angiogenesis by increasing the synthesis of PAI-1. This, in turn, inhibits PA activity and, therefore, plasmin generation, which is essential for the invasive aspect of angiogenesis.

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Section: Discussionmentioning

confidence: 99%

Mechanism of action of angiostatic steroids: Suppression of plasminogen activator activity via stimulation of plasminogen activator inhibitor synthesis

Blei

Mignatti

et al. 1993

Journal Cellular Physiology

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132

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“…After day 5, wound tensile strength increases as collagen molecules are deposited in the wound matrix. Water resorption allows these collagen molecules to lie in closer proximity, forming larger bundles, and cross linkingthus adding to the increase in stiffness and tensile strength (43,44).…”

Section: Comparative Measurements Of Porcine Wound Tissuementioning

confidence: 99%

Ultrasound assessment of skin and wound tissue: comparison with histology

Rippon

Springett

Walmsley

et al. 1998

Skin Research and Technology

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“…Autocrine and paracrine secretion of cytokines, metalloproteinases and related enzymes by keratinocytes, platelets, macrophages, and fibroblasts may have an important function in promoting wound closure and avoiding infection (Antoniades et al 1991(Antoniades et al , 1993DeBoer et al 1994;Gailit et al 1994;Kane et al 1991;Mignatti et al 1988;Riches 1988). Temporary use of biological coverings such as cadaver skin, human amniotic membranes and porcine skin may improve wound healing, but they are of limited benefit because of problems with sterility, difficult handling, risk of viral pathogens, and immune rejection by the host (De Riel 1984).…”

Section: Introductionmentioning

confidence: 98%

Frozen cultured sheets of human epidermal keratinocytes enhance healing of full-thickness wounds in mice

Tamaríz

Marsch-Moreno

Castro‐Muñozledo

et al. 1999

Cell and Tissue Research

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Sheets of cultured allogeneic human keratinocytes have been used for the treatment of burns and chronic leg ulcers but there has been no animal assay for the therapeutic action of these cultures. In order to analyze the effects of frozen cultures of human keratinocytes on wound healing, we have developed such an assay based on the rate of repair of full-thickness skin wounds in immunocompetent NMR1 mice. Reepithelialization of the control wounds, originating from the murine epithelium at the edge of the wound, occurred at a constant rate of advance of 150 microm/day. When frozen cultured human epidermal sheets were thawed at room temperature for 5-10 min and applied to the surface of the wound, the murine epithelium advanced at 267 microm/day. Most wounds treated with frozen cultures completely healed after 10 days, whereas most control wounds required 16 days. The accelerated reepithelialization did not depend on the presence of proliferative human keratinocytes in the frozen cultures. The cultures also promoted early formation of granulation tissue and laminin deposition over the surface of the wound bed. This simple assay should permit quantitative analysis of the effects on healing exerted not only by cultured cells, but also by proteins and small molecules.

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Role of Degradative Enzymes in Wound Healing

Cited by 13 publications

References 193 publications

Mechanism of action of angiostatic steroids: Suppression of plasminogen activator activity via stimulation of plasminogen activator inhibitor synthesis

Mechanism of action of angiostatic steroids: Suppression of plasminogen activator activity via stimulation of plasminogen activator inhibitor synthesis

Ultrasound assessment of skin and wound tissue: comparison with histology

Frozen cultured sheets of human epidermal keratinocytes enhance healing of full-thickness wounds in mice

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