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。

• 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

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

Keloids是皮肤异常，其特征是Dennis中胶原蛋白束过多的沉积。患有乳子状的患者不仅抱怨其整容外观，而且还抱怨与慢性炎症相关的连续瘙痒和氯气压痛。细胞外基质（ECM）的降解可能与酮类皮肤的膨胀相关的上调，而乳突组织的高代谢活性可能是由于基质金属蛋白酶（MMPS）活性增加所致。基于这些假设，我们检查了酮衍生的成纤维细胞和正常真皮成纤维细胞之间MMP-1，MMP-8和MMP-13表达的差异。由于类视黄素是MMP的潜在抑制剂在光照皮肤和癌症治疗中，我们还检查了维甲酸是否会影响毛类衍生的成纤维细胞MMP的表达。实时PCR和ELISA的结果。 mRNA和蛋白质水平。在添加维甲酸蛋白后，对对照组中的MMP-1 mRNA表达显着更新，而在Keloid组中未观察到对照组中的MMP-8 mRNA表达在三小时时在12小时时在峰值下进行显着更新，而在Keloid衍生的纤维纤维中未观察到显着变化。相反，在12小时后的峰值抑制下，乳突组中的MMP-13 mRNA表达明显抑制。维多甲酸的添加，而对照组中的MMP-13 mRNA表达并未显着改变。MMP-1和MMP-8的减少可能有助于Keloid组织中I型和III型胶原蛋白的积累，并且该机制可以通过与MMP-13的分子相互作用来调节。维甲酸似乎可以逆转乳突衍生的成纤维细胞中MMP的异常表达谱，例如MMP-13的表达显着升高，部分通过AP-1途径的失活。目前的结果表明，维甲酸在临床上可能在临床上可用于改善乳突中看到的慢性炎症，并防止酮组织扩展到圆周正常皮肤中。较少的

项目成果

Okazaki M, Yoshimura K, Suzuki Y, Uchida G, Kitano Y, Harii K: "The mechanism of epidermal hyperpigmentation in cafe-au-lait macules of neurofibromatosis type 1 (von Recklinghausen's disease) may be associated with dermal fibroblast-derived stem cell fact

Okazaki M、Yoshimura K、Suzuki Y、Uchida G、Kitano Y、Harii K：“1 型神经纤维瘤病（冯·雷克林豪森病）的牛奶咖啡斑表皮色素沉着过度的机制可能与真皮成纤维细胞来源的干细胞有关

Okazaki M, Yoshimura K, Uchida a Harii K: "Elevated expression of Hepatocyte and Keratinocyte Growth Factor in cultured buccal-mucosa-derived fibroblasts compared with normal-skin-derived fibroblasts."Journal of Dermatological Science. 30. 108-115 (2002)

Okazaki M、Yoshimura K、Uchida a Harii K：“与正常皮肤来源的成纤维细胞相比，培养的颊粘膜来源的成纤维细胞中肝细胞和角质形成细胞生长因子的表达升高。”皮肤病学杂志。

Yoshimura K, et al.: "The Effect of two Episodes of denervation"Plast Reconstr. Surg. 109. 212-219 (2002)

Yoshimura K 等人：“两次去神经支配的效果”Plast Reconstr。

Okazaki M, Yoshimura K, Uchida a Harii K.: "Correlation between age and the secretions of melanocyte-stimulating cytokines in cultured keratinocytes and fibroblasts."British Journal of Dermatology. (in press).

Okazaki M、Yoshimura K、Uchida a Harii K.：“年龄与培养的角质形成细胞和成纤维细胞中黑素细胞刺激细胞因子的分泌之间的相关性。”英国皮肤病学杂志。

K Yoshimura, et al.: "Clinical trial of depigmenting treatment"Derm Surg.. (in press). (2003)

K Yoshimura 等人：“脱色治疗的临床试验”Derm Surg..（印刷中）。