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

疤痕疙瘩和增生性疤痕基因治疗开发的研究。

基本信息

批准号：
14370570
负责人：
YOSHIMURA Kotaro
金额：
$ 7.68万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370570/
关键词：
keloid fibroblast MMP skin retinoid tretinoin retinoic acid レノイドコラゲナーゼ繊維芽細胞 mRNA

项目摘要

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

疤痕疙瘩是一种皮肤异常，其特征是真皮层中胶原束过度沉积。患有疤痕疙瘩的患者不仅抱怨其外观，而且还抱怨与慢性炎症相关的持续瘙痒和/或压痛。与疤痕疙瘩向周围皮肤的扩张有关，疤痕疙瘩组织的高代谢活性可能是由于基质金属蛋白酶（MMP）活性增加所致。基于这些假设，我们检查了差异。由于类视黄醇在治疗光老化皮肤和癌症中是 MMP 的有效抑制剂，因此我们还研究了维A酸是否影响 MMP。实时PCR和ELISA结果显示MMP-13显着上调以及瘢痕疙瘩来源的成纤维细胞中 MMP-1 和 MMP-8 的 mRNA 和蛋白水平显着下调，添加维A酸后对照组的 MMP-1 mRNA 表达显着上调，而没有显着变化。瘢痕疙瘩组观察到：对照组 MMP-8 mRNA 表达显着上调，维A酸在 12 小时达到峰值，而瘢痕疙瘩来源的 MMP-8 mRNA 表达没有观察到明显变化。相比之下，瘢痕疙瘩组异常升高的MMP-13 mRNA表达在添加维A酸后12小时出现峰值抑制，而对照组MMP-13 mRNA表达没有显着降低。 MMP-1 和 MMP-8 中的维A酸可能有助于疤痕组织中 I 型和 III 型胶原的积累，并且这种机制可能通过与 MMP-13 的分子相互作用来调节。部分通过 AP-1 通路失活，逆转瘢痕疙瘩来源的成纤维细胞中 MMP 的异常表达谱，例如 MMP-13 的表达显着升高。目前的结果表明，维A酸在临床上可用于改善瘢痕疙瘩和慢性炎症。防止疤痕组织扩展到周围正常皮肤。