The role of keratinocyte growth factor in melanogenesis: a possible mechanism for the initiation of solar lentigines
The role of keratinocyte growth factor in melanogenesis: a possible mechanism for the initiation of solar lentigines
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DOI：
10.1111/j.1600-0625.2009.00957.x
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发表时间：
2010-10-01
影响因子：
3.6
通讯作者：
Lin, Connie B.
中科院分区：
文献类型：
--
作者：
Chen, Nannan;Hu, Yaping;Lin, Connie B.
日光雀斑(SLS)是一种色素沉着的病变，出现在皮肤暴露在阳光下的区域，与衰老有关。SL引发的分子机制尚不完全清楚。中波紫外线(UVB)刺激角质形成细胞产生白介素1α(IL-1α)，进而诱导角质形成细胞生长因子(KGF)的分泌，因此，我们研究了它们在SLS诱导中的可能作用。我们发现，KGF增加了有色表皮和人类皮肤外植体中的色素产生。此外，UVB辐射增加了KGF的表达，KGF处理诱导了原代黑素细胞酪氨酸酶(TYR)的表达。KGF诱导的色素变化在着色的尤卡坦猪和移植到免疫缺陷小鼠的人皮肤上得到证实。在这两个模型系统中，KGF单独或与IL-1α联合局部治疗，可导致体内形成色素沉着增加和网脊延长的色素沉着病变，这与人类SLS的组织学特征相似。初步的人皮肤免疫组织化学分析显示，在SL皮损中KGF适度增加，KGF受体(KGFR)强烈诱导。综上所述，KGF可在体外和体内增加色素的产生和沉积。此外，我们首次展示了体内产生与人类SLS组织结构相似的色素沉着病变，并表明KGF/KGFR参与了人类SLS的分子病理学。
Solar lentigines (SLs) are hyperpigmentary lesions presented on sun-exposed areas of the skin and associated with ageing. The molecular mechanism of SL initiation is not completely understood. Ultraviolet B (UVB) stimulates keratinocytes to produce interlukin-1 alpha (IL-1 alpha), which then induces keratinocyte growth factor (KGF) secretion; therefore, we examined their possible roles in the induction of SLs. We found that KGF increases pigment production in both pigmented epidermal equivalents and human skin explants. In addition, UVB exposure increases KGF expression, and KGF treatment induces tyrosinase (TYR) expression in primary melanocytes. The KGF-induced pigmentary changes were confirmed using pigmented Yucatan swine, and human skins grafted onto immuno-deficient mice. In both model systems, the topical treatment with KGF, alone or in combination with IL-1 alpha, resulted in the in vivo formation of hyperpigmentary lesions with increased pigment deposition and elongated rete ridges, which resemble the histological features of human SLs. Preliminary immunohistochemical analysis of human skins showed a moderate increase in KGF, and a strong induction in KGF receptor (KGFR) in SL lesions. In summary, KGF increases pigment production and deposition in vitro and in vivo. Moreover, we show for the first time the in vivo generation of hyperpigmentary lesions with histological resemblance to human SLs and indicate the involvement of KGF/KGFR in the molecular pathology of human SLs.