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

瘢痕疙瘩是一种皮肤异常，其特征是丹尼斯胶原纤维束过度沉积。瘢痕疙瘩患者不仅抱怨他们的外观，而且还抱怨与慢性炎症有关的持续瘙痒和/或压痛。细胞外基质（ECM）的降解可能与瘢痕疙瘩向周围皮肤的扩展相关，并且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）活性增加。基于这些假设，我们研究了瘢痕疙瘩来源的成纤维细胞和正常皮肤成纤维细胞之间MMP-1、MMP-8和MMP-13表达的差异。由于类维生素A在光老化皮肤和癌症的治疗中是MMPs的有效抑制剂，我们还研究了维甲酸是否影响瘢痕疙瘩来源的成纤维细胞的MMPs表达。实时PCR和ELISA的结果表明，MMP-13的表达显著上调，而MMP-13的表达显著下调。 ...更多信息 MMP-1和MMP-8在瘢痕疙瘩来源的成纤维细胞中的mRNA和蛋白水平。对照组MMP-1 mRNA表达在加入维甲酸后显著上调，而瘢痕疙瘩组未观察到显著变化;对照组MMP-8 mRNA表达在加入维甲酸后显著上调，12 h达到峰值，而瘢痕疙瘩来源的成纤维细胞未观察到显著变化。而瘢痕疙瘩组MMP-13 mRNA表达明显降低，12 h达高峰。MMP-1和MMP-8的表达降低可能与瘢痕疙瘩组织中I型和III型胶原的积累有关，其机制可能与MMP-13的分子相互作用有关。维甲酸似乎逆转了瘢痕疙瘩来源的成纤维细胞中MMP-13的异常表达，如MMP-13的表达显著升高，部分原因是AP-1通路的失活。目前的结果表明，维甲酸可能是临床上有用的，以改善瘢痕疙瘩中看到的慢性炎症，并防止瘢痕疙瘩组织扩展到周围正常皮肤。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