Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Exp Cell Res. 2021 Jul 1;404(1):112618. doi: 10.1016/j.yexcr.2021.112618. Epub 2021 May 7.
Androgenetic alopecia (AGA) is the most common type of hair loss dysfunction. Secreted frizzled related protein 1 (SFRP1) is found to be associated with hair loss, but its role in AGA and the regulation mechanism of its transcription level is unclear. The aim of our study is to explore the expression of SFRP1 in AGA samples and its transcriptional mechanism. Male frontal and occipital scalp hair follicles from AGA patients were collected, and human dermal papilla cells (DPCs) were isolated and cultured. SFRP1 gene was cloned and constructed into recombinant plasmids to perform dual-luciferase reporter assay. Transcription factor binding sites were predicted through the Jaspar website and further confirmed by the chromatin immunoprecipitation (ChIP) assay. Expression of genes in DPCs was determined by immunofluorescence (IF) staining, quantitative real-time PCR (qRT-PCR) and western blotting. Our findings showed that SFRP1 was highly expressed in DPCs of AGA patients. The core promoter region of SFRP1 was from -100 to +50 bp and was found to be positively regulated by forkhead box C1 (FOXC1), a transcription factor related to hair growth, both at mRNA and protein level in DPCs. Our study suggests that FOXC1 plays an important role in regulating SFRP1 transcription, which may provide new insights into the development of therapeutic strategies for the treatment of AGA.
雄激素性脱发（AGA）是最常见的脱发功能障碍类型。分泌卷曲相关蛋白 1（SFRP1）与脱发有关，但它在 AGA 中的作用及其转录水平的调节机制尚不清楚。我们的研究旨在探讨 SFRP1 在 AGA 样本中的表达及其转录机制。从 AGA 患者的男性额部和枕部头皮毛囊中采集 SFRP1 基因并构建重组质粒，进行双荧光素酶报告基因检测。通过 Jaspar 网站预测转录因子结合位点，并通过染色质免疫沉淀（ChIP）实验进一步验证。通过免疫荧光（IF）染色、定量实时 PCR（qRT-PCR）和 Western blot 检测 DPCs 中基因的表达。我们的研究结果表明，SFRP1 在 AGA 患者的 DPCs 中高表达。SFRP1 的核心启动子区域位于-100 至+50 bp 处，发现在 DPCs 中，与头发生长相关的转录因子叉头框 C1（FOXC1）在 mRNA 和蛋白水平上均正向调节 SFRP1 的转录。我们的研究表明，FOXC1 在调节 SFRP1 转录中起重要作用，这可能为 AGA 治疗策略的开发提供新的思路。
