Department of Dermatology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Genomic Medicine and Bioinformatic Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Front Immunol. 2021 May 6;12:600017. doi: 10.3389/fimmu.2021.600017. eCollection 2021.
Epidermal growth factor (EGF) acts as a paracrine and autocrine mediator of cell proliferation and differentiation in various types of epithelial cells, such as sebocytes, which produce the lipid-rich sebum to moisturize the skin. However, sebum lipids direct contact and by penetrating through the epidermis may have regulatory roles on epidermal and dermal cells as well. As EGF receptor (EGFR) is expressed throughout the proliferating and the lipid-producing layers of sebaceous glands (SGs) in healthy and acne-involved skin, we investigated the effect of EGF on SZ95 sebocytes and how it may alter the changes induced by palmitic acid (PA), a major sebum component with bioactive roles. We found that EGF is not only a potent stimulator of sebocyte proliferation, but also induces the secretion of interleukin (IL)6 and down-regulates the expression of genes involved in steroid and retinoid metabolism. Importantly, when applied in combination with PA, the PA-induced lipid accumulation was decreased and the cells secreted increased IL6 levels. Functional clustering of the differentially regulated genes in SZ95 sebocytes treated with EGF, PA or co-treated with EGF+PA further confirmed that EGF may be a potent inducer of hyperproliferative/inflammatory pathways (IL1 signaling), an effect being more pronounced in the presence of PA. However, while a group of inflammatory genes was up-regulated significantly in EGF+PA co-treated sebocytes, PA treatment in the absence of EGF, regulated genes only related to cell homeostasis. Meta-analysis of the gene expression profiles of whole acne tissue samples and EGF- and EGF+PA -treated SZ95 sebocytes showed that the EGF+PA co-activation of sebocytes may also have implications in disease. Altogether, our results reveal that PA-induced lipid accumulation and inflammation can be modulated by EGF in sebocytes, which also highlights the need for system biological approaches to better understand sebaceous (immuno)biology.
表皮生长因子（EGF）作为一种旁分泌和自分泌介质，在各种类型的上皮细胞中促进细胞增殖和分化，例如产生富含脂质的皮脂以滋润皮肤的皮脂腺细胞。然而，皮脂脂质直接接触并穿透表皮，也可能对表皮和真皮细胞具有调节作用。由于 EGF 受体（EGFR）在健康和痤疮相关皮肤的皮脂腺（SG）的增殖和产脂层中均有表达，我们研究了 EGF 对 SZ95 皮脂腺细胞的影响，以及它如何改变棕榈酸（PA）引起的变化，PA 是具有生物活性的皮脂主要成分。我们发现，EGF 不仅是皮脂腺细胞增殖的有力刺激物，还诱导白细胞介素（IL）6 的分泌，并下调参与类固醇和视黄醇代谢的基因的表达。重要的是，当与 PA 联合应用时，PA 诱导的脂质积累减少，细胞分泌的 IL6 水平增加。用 EGF、PA 或 EGF+PA 处理的 SZ95 皮脂腺细胞中差异调节基因的功能聚类进一步证实，EGF 可能是一种促过度增殖/炎症途径（IL1 信号）的有力诱导剂，在存在 PA 的情况下作用更为明显。然而，虽然在 EGF+PA 共处理的皮脂腺细胞中一组炎症基因显著上调，但在没有 EGF 的情况下，PA 处理仅调节与细胞内稳态相关的基因。对整个痤疮组织样本和用 EGF 和 EGF+PA 处理的 SZ95 皮脂腺细胞的基因表达谱进行的荟萃分析表明，EGF+PA 共激活皮脂腺细胞也可能与疾病有关。总之，我们的结果表明，PA 诱导的脂质积累和炎症可以被 EGF 在皮脂腺细胞中调节，这也强调了需要采用系统生物学方法来更好地理解皮脂腺（免疫）生物学。
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