Role of fibroblast-derived growth factors in regulating hyperpigmentation of solar lentigo
Role of fibroblast-derived growth factors in regulating hyperpigmentation of solar lentigo
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DOI：
10.1111/j.1365-2133.2010.09946.x
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发表时间：
2010-11-01
影响因子：
10.3
通讯作者：
Picardo, M.
中科院分区：
文献类型：
--
作者：
Kovacs, D.;Cardinali, G.;Picardo, M.
背景皮肤色素沉着受到复杂的黑色素生成网络的调节，其中角质形成细胞和成纤维细胞合成生长因子和细胞因子。日光性雀斑 (SL) 的特征是光损伤皮肤区域出现色素沉着过度病变。尽管 SL 与紫外线 (UV) 暴露有关，但这些斑点形成的机制尚未完全明确。 目的 分析成纤维细胞衍生生长因子、肝细胞生长因子 (HGF)、角质形成细胞生长因子 (KGF) 和干细胞因子 (SCF) 在 SL 色素沉着过度中的作用；评估成纤维细胞中发生的光老化过程是否可能导致这些细胞因子表达的改变；并研究KGF通过角质形成细胞特异性诱导黑色素细胞因子在调节色素沉着中的新的可能作用。方法我们对SL活检中的HGF、KGF和SCF进行了免疫组织化学分析。我们使用成纤维细胞诱导的光老化体外模型分析了这些细胞因子的 mRNA 表达。最后，我们评估了 KGF 对角质形成细胞 mRNA 和蛋白水平上黑色素细胞因子表达的影响。结果我们发现 SL 病变的真皮上层中 HGF、KGF 和 SCF 呈阳性染色，并且在光老化成纤维细胞中显着诱导这三种细胞因子。我们还证明了 KGF 对色素沉着的贡献，表明其能够特异性调节角质形成细胞中 SCF 的表达。 结论 成纤维细胞可能会被紫外线照射持续激活，释放黑色素生长因子；这种诱导性细胞因子网络通过角质形成细胞直接或间接发挥作用，可能导致 SL 色素沉着过度。
Background Cutaneous pigmentation is regulated by a complex melanogenic network in which both keratinocytes and fibroblasts synthesize growth factors and cytokines. Solar lentigo (SL) is characterized by hyperpigmented lesions occurring on photodamaged skin areas. Despite the association of SL to ultraviolet (UV) exposure, the mechanisms underlying the development of these spots are not completely defined.Objectives To analyse the involvement of the fibroblast-derived growth factors, hepatocyte growth factor (HGF), keratinocyte growth factor (KGF) and stem cell factor (SCF) in SL hyperpigmentation; to evaluate whether the photoageing process occurring in fibroblasts could be responsible for the altered expression of these cytokines; and to investigate a new possible role of KGF in regulating pigmentation through the specific induction of melanogenic cytokines by keratinocytes.Methods We performed immunohistochemical analysis of HGF, KGF and SCF on SL biopsies. We analysed the mRNA expression of these cytokines using an in vitro model of photoageing induced on fibroblasts. Finally, we evaluated the effects of KGF on the expression of melanogenic cytokines at the mRNA and protein levels on keratinocytes.Results We found positive staining for HGF, KGF and SCF in the upper dermis of SL lesions and a significant induction of the three cytokines in photoaged fibroblasts. We also demonstrated the contribution of KGF to pigmentation, showing its ability specifically to modulate the expression of SCF in keratinocytes.Conclusions Fibroblasts may be persistently activated by UV exposure to release melanogenic growth factors; this inducible cytokine network acts both directly and indirectly through keratinocytes and may contribute to the hyperpigmentation of SL.