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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.
Highlights
Sebaceous glands are holocrine glands concentrated in the face and scalp and located on most surfaces of the human body
Our findings demonstrated that HDAC1 plays a critical role in reducing sterol regulatory-binding protein 1 (SREBP1) transcription, leading to decreased sebaceous lipogenesis
Treatment with insulin and TO901317 for 72 h resulted in significant increases in lipid droplet accumulation in the cytoplasm, as visualized using Oil Red O and Nile red stainings (Figure 1A and Figure S1)
Summary
Sebaceous glands are holocrine glands concentrated in the face and scalp and located on most surfaces of the human body. Sebocytes, specialized sebaceous gland cells, produce and secrete lipids, consisting of triglycerides, fatty acids, wax esters, squalene, cholesterol esters, and cholesterol [1]. Sebaceous lipids and cell debris are constituents of sebum, which protects the skin by balancing moisture and providing innate immunity. Excessive sebum excretion is a major factor in the pathophysiology of acne vulgaris [2]. Sebum production is dependent on de novo lipogenesis in sebocytes [3]. Recent studies have shown that sebaceous lipogenesis is regulated by various physiological factors, such as hormones and nuclear receptors. Insulin was found to stimulate sebaceous lipogenesis and differentiation [4,5]. Liver X receptors (LXRs) play major roles
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