Krüppel 样因子 4（KLF4）通过调节 SREBP1 的表达促进永生化人皮脂腺细胞的脂质生成。
Krüppel-like factor 4 (KLF4) facilitates lipid production in immortalized human sebocytes via regulating the expression of SREBP1.
机构信息
Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, School of Medicine, Shenzhen University, Shenzhen, 518060, China; Department of Dermatology, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, 518052, China.
Department of Dermatology, Chungnam National University School of Medicine, Chungnam National University Hospital, Daejeon, 35015, South Korea.
出版信息
Biochem Biophys Res Commun. 2023 Jul 30;667:146-152. doi: 10.1016/j.bbrc.2023.05.043. Epub 2023 May 14.
BACKGROUND
Acne is associated with the excessive production of sebum, a complex mixture of lipids, in the sebaceous glands. The transcription factor Krüppel-like factor 4 (KLF4) plays an important role in skin morphogenesis, but its role in sebum production by sebocytes is not well known.
PURPOSE
In this study, we investigated the possible action mechanism of KLF4 during calcium-induced lipogenesis in immortalized human sebocytes.
METHODS
Sebocytes were treated with calcium, and lipid production was confirmed by thin-layer chromatography (TLC) and Oil Red O staining. To investigate the effect of KLF4, sebocytes were transduced with the KLF4-overexpressing adenovirus, and then lipid production was evaluated.
RESULTS
Calcium treatment resulted in increased sebum production in terms of squalene synthesis in sebocytes. In addition, calcium increased the expression of lipogenic regulators such as sterol-regulatory element binding protein 1 (SREBP1), sterol-regulatory element binding protein 2 (SREBP2), and stearoyl-CoA desaturase (SCD). Similarly, the expression of KLF4 was increased by calcium in sebocytes. To investigate the effect of KLF4, we overexpressed KLF4 in sebocytes using recombinant adenovirus. As a result, KLF4 overexpression increased the expression of SREBP1, SREBP2, and SCD. Parallel to this result, lipid production was also increased by KLF4 overexpression. Chromatin immunoprecipitation revealed the binding of KLF4 to the SREBP1 promoter, indicating that KLF4 may directly regulate the expression of lipogenic regulators.
CONCLUSION
These results suggest that KLF4 is a novel regulator of lipid production in sebocytes.
背景
痤疮与皮脂腺中皮脂的过度产生有关，皮脂是一种复杂的脂质混合物。转录因子 Krüppel 样因子 4（KLF4）在皮肤形态发生中起重要作用，但它在皮脂腺中皮脂产生中的作用尚不清楚。
目的
本研究旨在探讨 KLF4 在人永生化皮脂腺细胞钙诱导脂肪生成过程中的可能作用机制。
方法
用钙处理皮脂腺细胞，并通过薄层层析（TLC）和油红 O 染色确认脂质生成。为了研究 KLF4 的作用，用 KLF4 过表达腺病毒转导皮脂腺细胞，然后评估脂质生成。
结果
钙处理导致皮脂腺细胞中角鲨烯合成的皮脂产生增加。此外，钙增加了脂肪生成调节剂的表达，如固醇调节元件结合蛋白 1（SREBP1）、固醇调节元件结合蛋白 2（SREBP2）和硬脂酰辅酶 A 去饱和酶（SCD）。同样，钙也增加了皮脂腺细胞中 KLF4 的表达。为了研究 KLF4 的作用，我们使用重组腺病毒过表达 KLF4 在皮脂腺细胞中。结果，KLF4 过表达增加了 SREBP1、SREBP2 和 SCD 的表达。与此结果平行，KLF4 过表达也增加了脂质生成。染色质免疫沉淀显示 KLF4 与 SREBP1 启动子结合，表明 KLF4 可能直接调节脂肪生成调节剂的表达。
结论
这些结果表明 KLF4 是皮脂腺细胞中脂质生成的一种新的调节因子。
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