Premanand Adaikalasamy, Reena Rajkumari Baskaran
Department of Integrative Biology, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu, India.
Front Med (Lausanne). 2023 Jun 9;10:1108358. doi: 10.3389/fmed.2023.1108358. eCollection 2023.
Androgenetic alopecia (AGA) is a common progressive scalp hair loss disorder that leads to baldness. This study aimed to identify core genes and pathways involved in premature AGA through an approach.
Gene expression data (GSE90594) from vertex scalps of men with premature AGA and men without pattern hair loss was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between the bald and haired samples were identified using the package in R. Gene ontology and Reactome pathway enrichment analyses were conducted separately for the up-regulated and down-regulated genes. The DEGs were annotated with the AGA risk loci, and motif analysis in the promoters of the DEGs was also carried out. STRING Protein-protein interaction (PPI) and Reactome Functional Interaction (FI) networks were constructed using the DEGs, and the networks were analyzed to identify hub genes that play could play crucial roles in AGA pathogenesis.
The study revealed that genes involved in the structural makeup of the skin epidermis, hair follicle development, and hair cycle are down-regulated, while genes associated with the innate and adaptive immune systems, cytokine signaling, and interferon signaling pathways are up-regulated in the balding scalps of AGA. The PPI and FI network analyses identified 25 hub genes namely CTNNB1, EGF, GNAI3, NRAS, BTK, ESR1, HCK, ITGB7, LCK, LCP2, LYN, PDGFRB, PIK3CD, PTPN6, RAC2, SPI1, STAT3, STAT5A, VAV1, PSMB8, HLA-A, HLA-F, HLA-E, IRF4, and ITGAM that play crucial roles in AGA pathogenesis. The study also implicates that Src family tyrosine kinase genes such as LCK, and LYN in the up-regulation of the inflammatory process in the balding scalps of AGA highlighting their potential as therapeutic targets for future investigations.
雄激素性脱发（AGA）是一种常见的进行性头皮脱发疾病，可导致秃顶。本研究旨在通过一种方法确定参与早发性AGA的核心基因和通路。
从基因表达综合数据库下载早发性AGA男性和无型脱发男性头顶头皮的基因表达数据（GSE90594）。使用R中的软件包鉴定秃发和有发样本之间的差异表达基因（DEG）。分别对上调和下调基因进行基因本体论和Reactome通路富集分析。将DEG与AGA风险位点进行注释，并对DEG启动子进行基序分析。使用DEG构建STRING蛋白质-蛋白质相互作用（PPI）和Reactome功能相互作用（FI）网络，并对网络进行分析以鉴定在AGA发病机制中可能起关键作用的枢纽基因。
该研究表明，在AGA的秃发头皮中，参与皮肤表皮结构组成、毛囊发育和毛发周期的基因下调，而与先天和适应性免疫系统、细胞因子信号传导和干扰素信号通路相关的基因上调。PPI和FI网络分析确定了25个枢纽基因，即CTNNB1、EGF、GNAI3、NRAS、BTK、ESR1、HCK、ITGB7、LCK、LCP2、LYN、PDGFRB、PIK3CD、PTPN6、RAC2、SPI1、STAT3、STAT5A、VAV1、PSMB8、HLA-A、HLA-F、HLA-E、IRF4和ITGAM，它们在AGA发病机制中起关键作用。该研究还表明，Src家族酪氨酸激酶基因，如LCK和LYN，在AGA秃发头皮的炎症过程上调中起作用，突出了它们作为未来研究治疗靶点的潜力。
