Dermal fibroblasts seem critical for epidermal maturation and differentiation and recent work demonstrated that diseased fibroblasts may drive pathophysiological processes. Nevertheless, still very little is known about the actual crosstalk between epidermal keratinocytes and dermal fibroblasts and the impact of dermal fibroblasts on epidermal maturation and differentiation. Aiming for a more fundamental understanding of the impact of the cellular crosstalk between keratinocytes and fibroblasts on the skin homeostasis, we generated full-thickness skin equivalents with and without fibroblasts and subsequently analysed them for the expression of skin differentiation markers, their barrier function, skin lipid content and epidermal cell signalling. Skin equivalents without fibroblasts consistently showed an impaired differentiation and dysregulated expression of skin barrier and tight junction proteins, increased skin permeability, and a decreased skin lipid/protein ratio. Most interestingly, impaired Ras/Raf/ERK/MEK signalling was evident in skin equivalents without fibroblasts. Our data clearly indicate that the epidermal-dermal crosstalk between keratinocytes and fibroblasts is critical for adequate skin differentiation and that fibroblasts orchestrate epidermal differentiation processes.

中文翻译：

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表皮角质形成细胞和真皮成纤维细胞之间的细胞间串扰对皮肤稳态的影响。

皮肤成纤维细胞对于表皮的成熟和分化似乎至关重要，最近的研究表明，患病的成纤维细胞可能会推动病理生理过程。然而，对于表皮角质形成细胞与真皮成纤维细胞之间的实际串扰以及真皮成纤维细胞对表皮成熟和分化的影响知之甚少。为了对角质形成细胞和成纤维细胞之间的细胞串扰对皮肤稳态的影响有更基本的了解，我们生成了有或没有成纤维细胞的全厚度皮肤等效物，随后对其进行了皮肤分化标志物，屏障功能，皮肤表达的分析。脂质含量和表皮细胞信号传导。没有成纤维细胞的皮肤等同物始终显示出分化障碍和皮肤屏障和紧密连接蛋白的表达失调，皮肤通透性增加以及皮肤脂质/蛋白质比降低。最有趣的是，在没有成纤维细胞的皮肤等效物中，Ras / Raf / ERK / MEK信号受损明显。我们的数据清楚地表明，角质形成细胞和成纤维细胞之间的表皮-真皮串扰对于适当的皮肤分化至关重要，并且成纤维细胞协调表皮分化过程。