Chemical Characterization and Quantification of Proteoglycans in Human Post-Burn Hypertrophic and Mature Scars

Scott, Paul; Dodd, Carole M.; Tredget, E. E.; Ghahary, Aziz; Rahemtulla, Firoz

doi:10.1042/cs0900417

Cited by 100 publications

(78 citation statements)

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“…Several recent observations suggest the possibility that it acts as a physiological regulator of fibrogenesis in vivo [29,33]. If this is true, decorin can be said to suppress fibrous adhesion in a "physiological" manner.…”

Section: Discussionmentioning

confidence: 99%

Suppression of fibrous adhesion by proteoglycan decorin

Fukui¹,

Fukuda²,

Kojima³

et al. 2001

Journal Orthopaedic Research

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Small proteoglycan decorin is known to suppress the bioactivity of TGF-P through a competitive binding with the cell surface receptors for the cytokine. Based on this knowledge, we hypothesized that decorin could reduce the formation of fibrous adhesion, because our previous study showed the neutralizing antibody to TGF-Dl has that effect. An intra-articular adhesion model in the rabbit knee joint was employed in this study, and decorin was administered into the joint cavity continuously during the 4 weeks of the experiment. The results of the dose-response study demonstrated that decorin suppresses formation of fibrous adhesion in a dose-dependent manner. When the administration of decorin was limited to shorter periods, this effect was considerably impaired and the necessity of long-term administration was demonstrated. On the other hand, when administered together with TGF-PI, decorin still suppressed adhesion but to a lesser extent, and it was suggested that this proteoglycan could have other significant mechanism( s) to suppress adhesion besides the neutralization of TGF-0. Thus, the present study showed that decorin could inhibit adhesion formation by both TGF-f~ dependent and independent mechanisms. Considering that decorin exists ubiquitously in the body, its administration might be a promising approach to suppress adhesion.

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Section: Discussionmentioning

confidence: 99%

Suppression of fibrous adhesion by proteoglycan decorin

Fukui¹,

Fukuda²,

Kojima³

et al. 2001

Journal Orthopaedic Research

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“…30 This massive release of active mediators results in severe damage to the ECM. Most notably, increased activity of fibrogenic cytokines such as TGF-b1 leads to alterations in the collagen fiber network.…”

Section: Discussionmentioning

confidence: 99%

RGTA OTR4120, a heparan sulfate mimetic, is a possible long‐term active agent to heal burned skin

Garcia-Filipe

Barbier-Chassefière

Alexakis

et al. 2006

J Biomedical Materials Res

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Burn-related skin fibrosis leads to loss of tissue function and hypertrophic scar formation with damaging consequences for the patient. There is therefore a great need for an efficient agent to treat burned skin. We report that ReGeneraTing Agent (RGTA) reduces burn-induced skin alteration. The tissue-regenerating effect of RGTA OTR4120 was evaluated after 1-6 days and after 10 months in a rat skin burn model. This effect was also examined in vitro using fibroblasts isolated from control and 6-day-old burned skins. We measured production of dermal collagen I, III, and V and activities of metalloproteinases 2 and 9 (MMP-2 and MMP-9). Ratio of collagen III over collagen I production increased 6 days after the burn, because of a decrease in collagen I production. After 10 months, ratio of collagen III over collagen I in burn sites was still increased compared with control skin, because of an increase in collagen III production. Both abnormalities were corrected by OTR4120. OTR4120 increased pro-and active MMP-2 and MMP-9, compared with healthy and burned controls and therefore accelerated remodeling. Similar data were obtained with cultured fibroblasts from healthy and burned skins. OTR4120 enhanced healing in short-and long-term after burns, reducing the formation of fibrotic tissue, and then represents a potential agent to improve burned skin healing.

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“…Decorin, a small proteoglycan with one dermatan sulfate sugar chain, is normally prevalent in the dermal ECM. Decorin regulates collagen fibril, fiber and fiber-bundle organization and has been shown to be decreased by about 75% in hypertrophic scars (76). Decorin is able to bind and neutralize TGF-β, thus minimizing the stimulatory effects of this cytokine on collagen, fibronectin and glycosaminoglycan production (32).…”

Section: Matrix Remodeling/maturation Phasementioning

confidence: 99%

Hypertrophic Scarring and Keloids: Pathomechanisms and Current and Emerging Treatment Strategies

Gauglitz

Körting

Pavicic

et al. 2010

Mol Med

1,148

1,012

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Excessive scars form as a result of aberrations of physiologic wound healing and may arise following any insult to the deep dermis. By causing pain, pruritus and contractures, excessive scarring significantly affects the patient's quality of life, both physically and psychologically. Multiple studies on hypertrophic scar and keloid formation have been conducted for decades and have led to a plethora of therapeutic strategies to prevent or attenuate excessive scar formation. However, most therapeutic approaches remain clinically unsatisfactory, most likely owing to poor understanding of the complex mechanisms underlying the processes of scarring and wound contraction. In this review we summarize the current understanding of the pathophysiology underlying keloid and hypertrophic scar formation and discuss established treatments and novel therapeutic strategies.

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Chemical Characterization and Quantification of Proteoglycans in Human Post-Burn Hypertrophic and Mature Scars

Cited by 100 publications

References 0 publications

Suppression of fibrous adhesion by proteoglycan decorin

Suppression of fibrous adhesion by proteoglycan decorin

RGTA OTR4120, a heparan sulfate mimetic, is a possible long‐term active agent to heal burned skin

Hypertrophic Scarring and Keloids: Pathomechanisms and Current and Emerging Treatment Strategies

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