Wei Ziyu, Chen Guangjie, Hu Tingting, Mo Xiaohui, Hou Xiaoxiao, Cao Ke, Wang Lanqi, Pan Zhanyan, Wu Qiong, Li Xin, Ye Feng, Zouboulis Christos C, Ju Qiang
Department of Dermatology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China.
Department of Immunology and Microbiology, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China.
J Dermatol Sci. 2021 Sep;103(3):156-166. doi: 10.1016/j.jdermsci.2021.07.010. Epub 2021 Jul 24.
Acne vulgaris is a prevalent skin disease lacking effective and well-tolerated treatment. An earlier study indicated that resveratrol (RVT) has therapeutic effects in acne patients through unknown mechanisms.
To evaluate the effects of RVT on linoleic acid (LA)-induced lipogenesis and peptidoglycan (PGN)-induced inflammation in cultured SZ95 sebocytes in vitro, and to investigate the underlying mechanisms.
RNA-sequencing was used to analyze the whole transcriptome. Nile red staining was used to detect intracellular neutral lipids, whereas lipidomics was used to investigate changes in the lipid profile in sebocytes. Interleukin (IL)-1β and IL-6 mRNA and protein levels were assessed through quantitative real-time PCR and Enzyme-linked immunosorbent assay, respectively. Western blot was used to evaluate the expression of lipogenesis-related proteins, the inflammatory signaling pathway, and the AMP-activated protein kinase (AMPK) pathway. Further, specific small interfering RNA (siRNA) was used to knockdown sirtuin-1 (SIRT1) expression.
RVT inhibited the lipogenesis-related pathway and nuclear factor-kappa B (NF-κB) signaling pathway in SZ95 sebocytes. It also downregulated LA-induced lipogenesis, the expression of lipid-related proteins, and the contents of unsaturated fatty acids. Besides, RVT promoted SIRT1 expression and deacetylation of the NF-κB p65 subunit, thereby lowering IL-1β and IL-6 secretion under PGN induction. Furthermore, pretreatment with AMPK inhibitor Compound C abolished RVT-mediated sebosuppressive and anti-inflammation effects. Meanwhile, SIRT1 silencing abrogated the anti-inflammatory potential of RVT.
In human SZ95 sebocytes, RVT exhibits sebosuppressive and anti-inflammatory effects partially through the AMPK pathway, which may justify the role of RVT treatment in acne vulgaris.
寻常痤疮是一种常见的皮肤病，缺乏有效且耐受性良好的治疗方法。一项早期研究表明，白藜芦醇（RVT）对痤疮患者具有治疗作用，但其机制尚不清楚。
评估RVT对体外培养的SZ95皮脂腺细胞中油酸（LA）诱导的脂肪生成和肽聚糖（PGN）诱导的炎症的影响，并探讨其潜在机制。
采用RNA测序分析全转录组。尼罗红染色用于检测细胞内中性脂质，而脂质组学用于研究皮脂腺细胞中脂质谱的变化。分别通过定量实时PCR和酶联免疫吸附测定评估白细胞介素（IL）-1β和IL-6的mRNA和蛋白水平。蛋白质印迹法用于评估脂肪生成相关蛋白、炎症信号通路和AMP激活蛋白激酶（AMPK）通路的表达。此外，使用特异性小干扰RNA（siRNA）敲低沉默调节蛋白1（SIRT1）的表达。
RVT抑制SZ95皮脂腺细胞中的脂肪生成相关通路和核因子-κB（NF-κB）信号通路。它还下调LA诱导的脂肪生成、脂质相关蛋白的表达以及不饱和脂肪酸的含量。此外，RVT促进SIRT1表达和NF-κB p65亚基的去乙酰化，从而降低PGN诱导下IL-1β和IL-6的分泌。此外，用AMPK抑制剂化合物C预处理可消除RVT介导的皮脂抑制和抗炎作用。同时，SIRT1沉默消除了RVT的抗炎潜力。
在人SZ95皮脂腺细胞中，RVT部分通过AMPK途径发挥皮脂抑制和抗炎作用，这可能解释了RVT治疗寻常痤疮的作用机制。
