Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8575, Japan; Division of Dermatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8575, Japan.
J Dermatol Sci. 2019 Mar;93(3):150-158. doi: 10.1016/j.jdermsci.2019.01.007. Epub 2019 Jan 26.
The main pathogenesis of acne vulgaris is increase in sebum production and abnormal keratinization of the hair infundibulum. The androgens are involved in acne pathogenesis by modulating sebaceous glands to enhance sebum production. However, the molecular mechanisms of abnormal keratinization of the hair infundibulum are not fully elucidated.
We hypothesized that the androgens affect the dermal fibroblasts, another androgen receptor-positive cells in the skin, resulting in abnormal keratinization through keratinocyte-fibroblast interaction.
We investigated effects of androgens and estrogens on growth factors expressions by RT-PCR and western blot analysis in human fibroblast (hFB), human keratinocyte (hKC), and fibroblast-keratinocyte co-culture. In vivo, we examined the growth factor expression in acne lesions compared to normal hair follicles by laser-assisted confocal microscope.
In vitro, androgens but not estrogens significantly increased amphiregulin (AREG), epiregulin (EREG), fibroblast growth factor (FGF) 10, and insulin-like growth factor binding protein (IGFBP) 5 mRNA and protein expressions in human fibroblasts but not in keratinocytes. In vivo, AREG, EREG, FGF10, and IGFBP5 were more abundant in acne lesion compared to normal facial skin. FGF10 suppressed cytokeratin 1 and cytokeratin 10 expression in hKC, which was along with the decreased ratio of cytokeratin 10 against cytokeratin 14 in acne lesions compared to normal facial skin. Also, DHT suppressed cytokeratin 1 and cytokeratin 10, in fibroblast-keratinocyte co-culture similarly to the effect of FGF10 to hKC.
These observations suggested that androgens enhance growth factors production from dermal fibroblasts, and growth factors from fibroblasts alter keratinocyte differentiation in acne lesion.
寻常痤疮的主要发病机制是皮脂分泌增加和毛囊异常角化。雄激素通过调节皮脂腺来增强皮脂分泌，参与痤疮的发病机制。然而，毛囊异常角化的分子机制尚未完全阐明。
我们假设雄激素作用于皮肤中另一种雄激素受体阳性细胞——真皮成纤维细胞，通过角质形成细胞和成纤维细胞的相互作用导致异常角化。
我们通过 RT-PCR 和 Western blot 分析研究了雄激素和雌激素对人成纤维细胞（hFB）、人角质形成细胞（hKC）和成纤维细胞-角质形成细胞共培养物中生长因子表达的影响。在体内，我们通过激光共聚焦显微镜检查了痤疮病变与正常毛囊中生长因子的表达。
体外，雄激素而非雌激素显著增加了人成纤维细胞中 Amphiregulin（AREG）、Epiregulin（EREG）、成纤维细胞生长因子（FGF）10 和胰岛素样生长因子结合蛋白 5（IGFBP5）的 mRNA 和蛋白表达，但对角质形成细胞无影响。在体内，AREG、EREG、FGF10 和 IGFBP5 在痤疮病变中比正常面部皮肤更为丰富。FGF10 抑制 hKC 中的细胞角蛋白 1 和细胞角蛋白 10 的表达，这与痤疮病变中细胞角蛋白 10 与细胞角蛋白 14 的比值较正常面部皮肤降低有关。此外，DHT 抑制成纤维细胞-角质形成细胞共培养物中细胞角蛋白 1 和细胞角蛋白 10 的表达，与 FGF10 对 hKC 的作用相似。
这些观察结果表明，雄激素增强了真皮成纤维细胞生长因子的产生，而来自成纤维细胞的生长因子改变了痤疮病变中角质形成细胞的分化。
