Garcia-Filipe S, Barbier-Chassefiere V, Alexakis C, Huet E, Ledoux D, Kerros M E, Petit E, Barritault D, Caruelle J P, Kern P
Laboratoire CRRET/CNRS UMR 7149, Faculté des Sciences, Université de Paris 12 Val de Marne, Avenue du Général de Gaulle 94010, Créteil Cedex, France.
J Biomed Mater Res A. 2007 Jan;80(1):75-84. doi: 10.1002/jbm.a.30874.
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.
烧伤相关的皮肤纤维化会导致组织功能丧失和肥厚性瘢痕形成，给患者带来不良后果。因此，迫切需要一种有效的药物来治疗烧伤皮肤。我们报告称，再生剂（RGTA）可减轻烧伤引起的皮肤改变。在大鼠皮肤烧伤模型中，于1 - 6天及10个月后评估了RGTA OTR4120的组织再生效果。还使用从对照皮肤和6日龄烧伤皮肤分离的成纤维细胞在体外进行了此项效果研究。我们测量了真皮胶原蛋白I、III和V的生成以及金属蛋白酶2和9（MMP - 2和MMP - 9）的活性。烧伤后6天，由于胶原蛋白I生成减少，胶原蛋白III与胶原蛋白I生成的比率增加。10个月后，与对照皮肤相比，烧伤部位胶原蛋白III与胶原蛋白I的比率仍因胶原蛋白III生成增加而升高。这两种异常情况均被OTR4120纠正。与健康和烧伤对照相比，OTR4120增加了前体和活性MMP - 2及MMP - 9，因此加速了重塑过程。从健康和烧伤皮肤培养的成纤维细胞也获得了类似数据。OTR4120在烧伤后的短期和长期均促进愈合，减少纤维化组织的形成，因此是一种有望改善烧伤皮肤愈合的药物。
