Wound degradomics – current status and future perspectives

Hermes, Olivia; Schlage, Pascal; Keller, Ulrich auf dem

doi:10.1515/bc.2011.092

Cited by 9 publications

(7 citation statements)

References 29 publications

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“…Matrix metalloproteinases (MMPs) are important in atherogenesis [ 106 ]. Endothelial dysfunction represents an alteration of normal endothelial function, which involves the loss of some structural features and/or function.…”

Section: Effects Of Nutraceuticals On Vascular Damagementioning

confidence: 99%

“…Endothelial dysfunction represents an alteration of normal endothelial function, which involves the loss of some structural features and/or function. The endothelium can be considered a true autocrine and paracrine organ, capable of secreting, in response to a large variety of signals, a number of chemical mediators [ 106 ]. The relationship between MMPs and traditional risk factors for cardiovascular disease (CVD) and any influence of lifestyle changes are largely unknown.…”

Section: Effects Of Nutraceuticals On Vascular Damagementioning

confidence: 99%

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Natural approaches in metabolic syndrome management

Patti¹,

Al-Rasadi²,

Giglio³

et al. 2018

aoms

110

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Metabolic syndrome (MetS) is characterized as a group of cardiometabolic risk factors that raise the risk for heart disease and other health problems, such as diabetes mellitus and stroke. Treatment strategies include pharmacologic interventions and supplementary (or “alternative”) treatments. Nutraceuticals are derived from food sources (isolated nutrients, dietary supplements and herbal products) that are purported to provide health benefits, in addition to providing basic nutritional value. Nutraceuticals are claimed to prevent chronic diseases, improve health, delay the aging process, increase life expectancy, and support the structure and function of the body. The study of the beneficial effects of nutraceuticals in patients with MetS, including product standardization, duration of supplementation and definition of optimal dosing, could help better define appropriate treatment. This review focuses on widely marketed nutraceuticals (namely polyphenols, omega-3 fatty acids, macroelements and vitamins) with clinically demonstrated effects on more than one component of MetS.

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Section: Effects Of Nutraceuticals On Vascular Damagementioning

confidence: 99%

Section: Effects Of Nutraceuticals On Vascular Damagementioning

confidence: 99%

Natural approaches in metabolic syndrome management

Patti¹,

Al-Rasadi²,

Giglio³

et al. 2018

aoms

110

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“…One of these methods, Terminal Amine Isotopic Labeling of Substrates (TAILS), was successfully applied in vitro to identify novel substrates of individual proteases (23)(24)(25)(26)(27)(28) and more recently also in vivo to systematically assess protease activity in complex tissue samples (29,30). TAILS has unique multiplexing capabilities and thus is particularly suited for analyzing the N-terminome at multiple time points after the stimulus (31) as required for the time-resolved analysis of proteolytic events at critical turning points after skin injury (32).…”

mentioning

confidence: 99%

In Vivo Assessment of Protease Dynamics in Cutaneous Wound Healing by Degradomics Analysis of Porcine Wound Exudates

Sabino

Hermes

Egli

et al. 2015

Molecular & Cellular Proteomics

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Proteases control complex tissue responses by modulating inflammation, cell proliferation and migration, and matrix remodeling. All these processes are orchestrated in cutaneous wound healing to restore the skin's barrier function upon injury. Altered protease activity has been implicated in the pathogenesis of healing impairments, and proteases are important targets in diagnosis and therapy of this pathology. Global assessment of proteolysis at critical turning points after injury will define crucial events in acute healing that might be disturbed in healing disorders. As optimal biospecimens, wound exudates contain an ideal proteome to detect extracellular proteolytic events, are noninvasively accessible, and can be collected at multiple time points along the healing process from the same wound in the clinics. In this study, we applied multiplexed Terminal Amine Isotopic Labeling of Substrates (TAILS) to globally assess proteolysis in early phases of cutaneous wound healing. By quantitative analysis of proteins and protein N termini in wound fluids from a clinically relevant pig wound model, we identified more than 650 proteins and discerned major healing phases through distinctive abundance clustering of markers of inflammation, granulation tissue formation, and re-epithelialization. TAILS revealed a high degree of proteolysis at all time points after injury by detecting almost 1300 N-terminal peptides in ϳ450 proteins. Quantitative positional proteomics mapped pivotal interdependent processing events in the blood coagulation and complement cascades, temporally discerned clotting and fibrinolysis during the healing process, and detected processing of complement C3 at distinct time points after wounding and by different proteases. Exploiting data on primary cleavage specificities, we related candidate proteases to cleavage events and revealed processing of the integrin adapter protein kindlin-3 by caspase-3, generating new hypotheses for protease-substrate relations in the healing skin wound in vivo.

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“…Wound cells respond to these changes (Hinz, 2010), and increasing evidence links wound pathogenesis to alterations in ECM compliance and mechanical tension within the wound bed (Wong et al, 2011). Such alterations may be caused by changes in cell-generated forces, defective ECM deposition, or mis-regulated proteolysis of the ECM (Hermes et al, 2011; Lancerotto et al, 2012; Shirakawa and Isseroff, 2005; Trengove et al, 1999; Wong et al, 2013). …”

Section: Potential Mechanisms Of Integrin-mediated Long-distance Sigmentioning

confidence: 99%

Integrin-mediated regulation of epidermal wound functions

et al. 2016

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During cutaneous wound healing, keratinocyte proliferation and migration are critical for re-epithelialization. In addition, the epidermis secretes growth factors, cytokines, proteases, and matricellular proteins into the wound microenvironment that modify the extracellular matrix and stimulate other wound cells that control the inflammatory response, promote angiogenesis, and facilitate tissue contraction and remodeling. Wound keratinocytes express at least seven different integrins - the major cell adhesion receptors for the extracellular matrix - that collectively control essential cell-autonomous functions to ensure proper re-epithelialization, including migration, proliferation, survival, and basement membrane assembly (Fig. 1, arrow 1). Moreover, it has become evident in recent years that some integrins can regulate paracrine signals from wound epidermis that stimulate other wound cells involved in angiogenesis, contraction and inflammation (Fig. 1, arrows 2 and 3). Importantly, it is likely that abnormal integrin expression or function in the epidermis contributes to wound pathologies such as over-exuberant healing (e.g., hypertrophic scar formation) or diminished healing (e.g., chronic wounds). In this review, we discuss current knowledge of integrin function in the epidermis, which implicates them as attractive therapeutic targets to promote wound healing or treat wound pathologies. We also discuss challenges that arise from the complex roles that multiple integrins play in wound epidermis, which may be regulated through extracellular matrix remodeling that determines ligand availability. Indeed, understanding how different integrin functions are temporally coordinated in wound epidermis, and which integrin functions go awry in pathological wounds, will be important to determine how best to target them clinically to achieve maximum therapeutic benefit.

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Wound degradomics – current status and future perspectives

Cited by 9 publications

References 29 publications

Natural approaches in metabolic syndrome management

Natural approaches in metabolic syndrome management

In Vivo Assessment of Protease Dynamics in Cutaneous Wound Healing by Degradomics Analysis of Porcine Wound Exudates

Integrin-mediated regulation of epidermal wound functions

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