Histone Deacetylase 1 Reduces Lipogenesis by Suppressing SREBP1 Transcription in Human Sebocyte Cell Line SZ95

International Journal of Molecular Sciences

卷:22

HyeSun Shin¹  SooIck Cho¹  DongHun Lee¹  MiHee Shin¹  MinKyoung Kim¹  JinHo Chung¹  Yuri Lee¹  ChristosC. Zouboulis² 

[1] Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Korea;

[2] Dessau Medical Center, Departments of Dermatology, Venereology, Allergology and Immunology, Faculty of Health Sciences Brandenburg, Brandenburg Medical School Theodor Fontane, 06847 Dessau, Germany;

关键词: histone deacetylase 1;    SREBP1;    lipogenesis;    sebocytes;    sebum;    histone acetylation;   

DOI  :  10.3390/ijms22094477

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown