RGTA OTR4120, a heparan sulfate mimetic, is a possible long-term active agent to heal burned skin.
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.
Garcia-Filipe
S
S
Laboratoire CRRET/CNRS UMR 7149, Faculté des Sciences, Université de Paris 12 Val de Marne, Avenue du Général de Gaulle 94010, Créteil Cedex, France.
Barbier-Chassefiere
V
V
Alexakis
C
C
Huet
E
E
Ledoux
D
D
Kerros
M E
ME
Petit
E
E
Barritault
D
D
Caruelle
J P
JP
Kern
P
P
D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D002056:Burns / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002921:Cicatrix / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D024022:Fibrillar Collagens / Q000096:biosynthesis; D006497:Heparan Sulfate / Q000494:pharmacology*; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051381:Rats; D011923:Rats, Nude; D012867:Skin / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects*
D024022:Fibrillar Collagens; D006497:Heparan Sulfate; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9