Molecular biological Research on mechanisms of refinoic acid for dermal wound healing and treatment of hyper pigmentation

维甲酸促进真皮伤口愈合和治疗色素沉着过度机制的分子生物学研究

• 批准号: 12470374
• 负责人: YOSHIMURA Kotaro
• 金额: $ 9.41万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470374/
• 关键词: retinoic acid; HB-EGF; melanin; melanocyte; hydroguinone; retinol; retinal; レチノイド; ハイドロコーチゾン; ケラチノサイト

The results suggested that RA neither have direct inhibitory effects on melanogenesis of melanocytes, nor influence the cell-cell interactions between melanocytes, keratinocytes and fibroblasts, such as paracrine actions with regard to melanin productions. The role of RA in bleaching treatments appears to be other specific actions, such as promotion of keratinocytes proliferation and acceleration of epidermal turnover. The results also revealed that HB-EGF mRNA expression was elevated dose-dependently with atRA, most at 12 hours. This elevation was more prominent in keratinocytes of confluent state than those of subconfluent state, suggesting differentiated keratinocytes are more subject to be stimulated by atRA with regard to HB-EGF expression than proliferating keratinocytes. Ral and Rol was found to upregulate HB-EGF when used at 100 μM to 1mM, to a similar extent of atRA at 1 to 10 μM. The capacity of retinoids to upregulate HB-EGF may be an important index to develop and seek an ideal synthetic retinoid, which has maximum benefits and minimal side effects.

结果表明，RA对黑素细胞的黑素合成没有直接的抑制作用，也不影响黑素细胞、角质形成细胞和成纤维细胞之间的细胞-细胞相互作用，如黑素合成的旁分泌作用。RA在漂白治疗中的作用似乎是其他特定的作用，如促进角质形成细胞增殖和加速表皮更新。结果还表明，HB-EGF mRNA的表达与atRA的剂量依赖性增加，在12小时最多。这种升高在融合状态的角质形成细胞中比亚融合状态的角质形成细胞中更为明显，这表明分化的角质形成细胞比增殖的角质形成细胞更容易受到atRA对HB-EGF表达的刺激。发现Ral和Rol在100 μM至1 mM浓度下上调HB-EGF，与atRA在1至10 μM浓度下的上调程度相似。类维生素A上调HB-EGF的能力可能是开发和寻求理想的合成类维生素A的重要指标，其具有最大的益处和最小的副作用。

项目成果

Yoshimura K, et al: "Experience of a strong bleaching treatment"Plastic Reconstructive Surgery. 105. 1097-1110 (2000)

Yoshimura K等人：“强力漂白治疗的经验”整形重建外科。

K.Yoshimura: "The Effect of Two Episodes of-"Plast.Reconstr.Surg.. 109. 212-219 (2002)

K.Yoshimura：“两集的效果-”Plast.Reconstr.Surg.. 109. 212-219 (2002)

K.Yoshimura: "The Effects of Two Episodes of 〜"Plast Reconstr. Surg. 109. 212-219 (2002)

K.Yoshimura：“〜”整形外科手术的两集的影响。 109. 212-219 (2002)

Y.Kitano: "Wound Healing of genetically diabetic"Arch Dermatol Res. 293. 515-521 (2001)

Y.Kitano：“遗传性糖尿病的伤口愈合”Arch Dermatol Res。

Gonda K, et al.: "Heterotopic ossification of degenerating rat skeletal muscle induced by adenovirus-mediated transfer of bone morphogenetic protein-2 gene"Bone Mineral Res.. 15. 1056-65 (2000)

Gonda K等人：“腺病毒介导的骨形态发生蛋白2基因转移诱导的退化大鼠骨骼肌的异位骨化”Bone Mineral Res.. 15. 1056-65 (2000)