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京尼平苷通过干细胞因子/c-Kit信号通路增强去甲肾上腺素处理的正常人表皮黑素细胞的黑素生成。

Geniposide enhances melanogenesis by stem cell factor/c-Kit signalling in norepinephrine-exposed normal human epidermal melanocyte.

作者信息

Lan Wen-Jun, Wang Hai-Yan, Lan Wei, Wang Ke-Yu

机构信息

Laboratory for Drug Discovery, Shandong Institute of Light Industry, Jinan, China.

出版信息

Basic Clin Pharmacol Toxicol. 2008 Jul;103(1):88-93. doi: 10.1111/j.1742-7843.2008.00251.x.

Abstract

Geniposide is an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis used as a Chinese traditional medicine for treatment of generalized vitiligo. Stem cell factor from keratinocyte recognizes and activates its receptor c-kit carried by melanocyte to potent enhance melanocytic melanogenesis that can be suppressed by norepinephrine. This study addresses the action and mechanism of geniposide enhancing melanogenesis in norepinephrine-exposed normal human epidermal melanocyte. Flow cytometry results from this study exhibited the augmentation effect of geniposide on production of c-kit receptor by norepinephrine-exposed normal human epidermal melanocyte. However, geniposide did not affect the production of stem cell factor by norepinephrine-exposed normal human epidermal keratinocyte assessed by cellular enzyme-linked immunosorbent assay (ELISA). ELISA indicated that at the presence of stem cell factor, geniposide was capable of elevating the level of extracellular signal-regulated kinase 1/2 phosphorylation within norepinephrine-exposed normal human epidermal melanocyte, which is known to be involved in stem cell factor/c-kit downstream signalling. And inhibition of c-kit with inhibitory antibody K44.2 completely blocked the increase in geniposide-stimulated extracellular signal-regulated kinase 1/2 phosphorylation. In addition, spectrophotometry demonstrated the enhancement effect of geniposide on melanogenesis (tyrosinase activity and melanin production) in norepinephrine-exposed normal human epidermal melanocyte at the presence of stem cell factor, which was blocked by c-kit inhibitory antibody K44.2. Data from this study suggest that geniposide can enhance melanogenesis by stem cell factor/c-kit signalling in which the expression of c-kit receptor is augmented in norepinephrine-exposed normal human epidermal melanocyte.

摘要

栀子苷是从中药栀子果实中分离得到的一种环烯醚萜苷,用于治疗泛发性白癜风。角质形成细胞分泌的干细胞因子可识别并激活黑素细胞携带的受体c-kit,从而有力地增强黑素细胞的黑素生成,而去甲肾上腺素可抑制这种生成。本研究探讨了栀子苷在去甲肾上腺素作用下的正常人表皮黑素细胞中促进黑素生成的作用及机制。本研究的流式细胞术结果显示,栀子苷对去甲肾上腺素作用下的正常人表皮黑素细胞中c-kit受体的产生具有增强作用。然而,通过细胞酶联免疫吸附测定(ELISA)评估,栀子苷对去甲肾上腺素作用下的正常人表皮角质形成细胞中干细胞因子的产生没有影响。ELISA表明,在存在干细胞因子的情况下,栀子苷能够提高去甲肾上腺素作用下的正常人表皮黑素细胞中细胞外信号调节激酶1/2的磷酸化水平,已知该激酶参与干细胞因子/c-kit的下游信号传导。用抑制性抗体K44.2抑制c-kit可完全阻断栀子苷刺激的细胞外信号调节激酶1/2磷酸化的增加。此外,分光光度法表明,在存在干细胞因子的情况下,栀子苷对去甲肾上腺素作用下的正常人表皮黑素细胞的黑素生成(酪氨酸酶活性和黑色素产生)具有增强作用,而c-kit抑制性抗体K44.2可阻断这种作用。本研究数据表明,栀子苷可通过干细胞因子/c-kit信号通路增强黑素生成,其中去甲肾上腺素作用下的正常人表皮黑素细胞中c-kit受体的表达增加。

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