Study for development of genetic therapy for keloid and hypertrophic scar.

瘢痕疙瘩是一种皮肤异常，其特征是dennis中胶原束过度沉积。瘢痕疙瘩患者不仅抱怨他们的外观，而且还抱怨持续的瘙痒和与慢性炎症相关的疼痛。细胞外基质（ECM）的降解可能与瘢痕疙瘩向周围皮肤的扩张有关，而瘢痕疙瘩组织的高代谢活性可能是由于基质金属蛋白酶（MMPs）活性的增加。基于这些假设，我们检测了瘢痕疙瘩源性成纤维细胞和正常真皮成纤维细胞之间MMP-1、MMP-8和MMP-13的表达差异。由于类维甲酸在治疗光老化皮肤和癌症中是MMPs的有效抑制剂，我们也研究了维甲酸是否影响瘢痕疙瘩源性成纤维细胞MMPs的表达。real-time PCR和ELISA结果显示瘢痕疙瘩源性成纤维细胞中MMP-13的mRNA和蛋白水平均显著上调，MMP-1和MMP-8的mRNA和蛋白水平均显著下调。添加维甲酸后，对照组MMP-1 mRNA表达显著上调，瘢痕疙瘩组无明显变化；对照组MMP-8 mRNA表达显著上调，在添加维甲酸后12小时达到峰值，而瘢痕疙瘩源性成纤维细胞无明显变化。瘢痕疙瘩组显著升高的MMP-13 mRNA表达明显受到抑制，并在12小时后达到峰值。而对照组的MMP-13 mRNA表达无显著变化。MMP-1和MMP-8的减少可能有助于瘢痕疙瘩组织中I型和III型胶原的积累，这一机制可能通过与MMP-13的分子相互作用来调节。维甲酸似乎可以逆转瘢痕疙瘩源性成纤维细胞中MMPs的异常表达谱，如MMP-13的表达显著升高，部分原因是AP-1通路失活。目前的结果表明，维甲酸可能在临床上有助于改善瘢痕疙瘩的慢性炎症，防止瘢痕疙瘩组织向周围正常皮肤扩张。少

Keloids are skin abnormalities that are characterized by excessive deposition of collagen bundles in the dennis. Patients with keloids complain not only about their cosmetic appearances, but also about continuous itching andlor tenderness associated with chronic inflammation. Degradation of extracellular matrix (ECM) may be upregulated associated with the expansion of keloids into circumferential skin, and high metabolic activity of keloid tissues may be due to increased matrix metalloproteinases (MMPs) activity. Based on these hypotheses, we examined differences in expressions of MMP-1, MMP-8, and MMP-13 between keloid-derived fibroblasts and normal dermal fibroblasts. Since retinoids are potent inhibitors of MMPs in the treatment of photoaged skin and cancers, we also examined whether or not tretinoin affects MMPs expressions of keloid-derived fibroblasts.The results of real-time PCR and ELISA demonstrated a significant upregulation of MMP-13 as well as significant downregulation of … More MMP-1 and MMP-8 in keloid-derived fibroblasts, both at mRNA and protein levels. MMP-1 mRNA expression in the control group was significantly upregulated after the addition of tretinoin, whereas no significant change was observed in the keloid group : MMP-8 mRNA expression in the control group was significantly upregulated with the peak at 12 hours by tretinoin, while no significant change was observed in the keloid-derived fibroblasts. In contrast, the remarkably elevated MMP-13 mRNA expression in the keloid group was significantly suppressed with the peak suppression at 12 hours after. addition of tretinoin, while MMP-13 mRNA expression in the control group was not significantly changed.The decrease in MMP-1 and MMP-8 may contribute to accumulation of type I and type III collagen in keloid tissues, and this mechanism may be modulated by molecular interaction with MMP-13. Tretinoin appeared to reverse the abnormal expression profile of MMPs in keloid-derived fibroblasts, such as markedly elevated expression of MMP-13, partly through inactivation of AP-1 pathway. The present results suggested that tretinoin may be clinically useful to improve chronic inflammation seen in keloids and prevent expansion of keloid tissues into circumferential normal skin. Less