Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea.
Department of Biomedical Sciences, Graduate School, Seoul National University, Seoul 03080, Korea.
Int J Mol Sci. 2021 Apr 25;22(9):4477. doi: 10.3390/ijms22094477.
Proper regulation of sebum production is important for maintaining skin homeostasis in humans. However, little is known about the role of epigenetic regulation in sebocyte lipogenesis. We investigated histone acetylation changes and their role in key lipogenic gene regulation during sebocyte lipogenesis using the human sebaceous gland cell line SZ95. Sebocyte lipogenesis is associated with a significant increase in histone acetylation. Treatment with anacardic acid (AA), a p300 histone acetyltransferase inhibitor, significantly decreased the lipid droplet number and the expression of key lipogenic genes, including sterol regulatory-binding protein 1 (SREBP1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). In contrast, treatment with trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, increased the expression of these genes. Global HDAC enzyme activity was decreased, and HDAC1 and HDAC2 expression was downregulated during sebaceous lipogenesis. Interestingly, HDAC1 knockdown increased lipogenesis through SREBP1 induction, whereas HDAC1 overexpression decreased lipogenesis and significantly suppressed promoter activity. HDAC1 and SREBP1 levels were inversely correlated in human skin sebaceous glands as demonstrated in immunofluorescence images. In conclusion, HDAC1 plays a critical role in reducing SREBP1 transcription, leading to decreased sebaceous lipogenesis. Therefore, HDAC1 activation could be an effective therapeutic strategy for skin diseases related to excessive sebum production.
皮脂的正常分泌对于维持人类皮肤的内环境稳定非常重要。然而，目前对于表观遗传调控在皮脂细胞脂肪生成中的作用知之甚少。我们使用人皮脂腺细胞系 SZ95 研究了组蛋白乙酰化变化及其在皮脂细胞脂肪生成过程中关键脂肪生成基因调控中的作用。皮脂细胞的脂肪生成与组蛋白乙酰化水平的显著增加有关。用 p300 组蛋白乙酰转移酶抑制剂 anacardic acid (AA) 处理可显著减少脂滴数量和关键脂肪生成基因的表达，包括固醇调节结合蛋白 1 (SREBP1)、脂肪酸合酶 (FAS) 和乙酰辅酶 A 羧化酶 (ACC)。相反，用组蛋白去乙酰化酶 (HDAC) 抑制剂 trichostatin A (TSA) 处理则增加了这些基因的表达。在皮脂细胞脂肪生成过程中，全球 HDAC 酶活性降低，HDAC1 和 HDAC2 的表达下调。有趣的是，HDAC1 敲低通过诱导 SREBP1 增加脂肪生成，而 HDAC1 过表达则减少脂肪生成，并显著抑制启动子活性。免疫荧光图像显示，在人皮肤皮脂腺中，HDAC1 和 SREBP1 的水平呈负相关。总之，HDAC1 在降低 SREBP1 转录方面发挥着关键作用，从而减少皮脂细胞的脂肪生成。因此，HDAC1 的激活可能是治疗与皮脂过度分泌相关的皮肤疾病的有效策略。
