Citation

  • Authors: Shin HS. et al.
  • Year: 2021
  • Journal: Int J Mol Sci 22 4477
  • Applications: in vitro / DNA / jetOPTIMUS
  • Cell type: SZ95

Method

HDAC1 overexpression was performed by transiently transfecting 80% confluent SZ95 cells with 1 µg pcDNA3 or HDAC1-Flag plasmid, using jetOPTIMUS® (Polyplus-transfection® SA, Illkirch, France) for 6 h. The medium was replaced with DMEM/Ham’s F12 medium (3:1) containing 2% FBS, insulin (10 µg/mL), and TO901317 (1 µM), and the cells were harvested after 48 h for mRNA and protein extraction or after 72 h for lipid analysis.

Abstract

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 SREBP1 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.

Pubmed