[关键词]
[摘要]
目的:探讨丝氨酸/苏氨酸激酶1(AKT1)、ATP合酶F1亚基(ATP5F1)及Bcl-2相关抗凋亡基因3(BAG3)三者在翼状胬肉发生发展中的表达差异及作用机制。
方法:通过GEO数据库获取翼状胬肉相关基因表达数据,筛选差异表达基因; 利用String数据库构建蛋白相互作用(PPI)网络,结合 Cytoscape软件筛选核心靶点; 采用GO和KEGG通路富集分析线粒体代谢相关通路特征。收集翼状胬肉手术患者的胬肉头部、体部组织标本,HE染色观察两组组织病理形态差异,免疫组化法检测AKT1、ATP5F1、BAG3的蛋白表达水平。
结果:GEO数据库分析共筛选出差异表达基因1 264个,其中上调585个、下调679个。GO富集分析显示,生物学过程、细胞组分及分子功能层面均存在线粒体相关通路的显著富集; KEGG富集分析以氧化磷酸化、化学致癌-活性氧簇通路差异最为显著。收集翼状胬肉手术患者28例28眼的胬肉头部、体部组织标本,其中男7例7眼,女21例21眼,平均年龄69.32±8.98岁。HE染色结果显示,胬肉头部较体部上皮细胞异型增生更明显、基质纤维排列更紊乱,且炎症细胞浸润更显著。免疫组化结果证实,AKT1、ATP5F1、BAG3在胬肉头部的蛋白表达水平显著低于体部(均P<0.05)。
结论:线粒体代谢相关基因AKT1、ATP5F1、BAG3在翼状胬肉中存在明显表达差异,且与病变组织的病理进展密切相关,其可能通过调控线粒体能量代谢参与翼状胬肉的发生发展,为该病的机制研究及靶向治疗提供新的实验依据与思路。
[Key word]
[Abstract]
AIM: To investigate expression differences and mechanism of action of serine/threonine kinase 1(AKT1), ATP synthase F1 subunit(ATP5F1), and Bcl-2-associated anti-apoptotic gene 3(BAG3)in the occurrence and progression of pterygium.
METHODS:Pterygium-related gene expression data were retrieved from GEO database to screen differentially expressed genes(DEGs). String and Cytoscape were used to construct protein-protein interaction(PPI)networks and identify core targets. GO/KEGG enrichment analyzed mitochondrial metabolic pathways. The pterygium samples(head/body)were collected; pathological features were evaluated by HE staining, and the expression of AKT1, ATP5F1, and BAG3 was detected via immunohistochemistry(IHC).
RESULTS:A total of 1 264 DEGs were identified(585 upregulated, 679 downregulated). GO analysis showed significant enrichment of mitochondrial pathways regarding to biological processes, cell components and molecular functions; KEGG analysis highlighted oxidative phosphorylation and chemical carcinogenesis-reactive oxygen species(ROS)pathways. The head and body pterygium samples were collected from 28 cases(28 eyes)that received pterygium surgery, including 7 males(7 eyes)and 21 females(21 eyes), with a mean age of 69.32±8.98 years. HE staining showed more severe dysplasia, disordered stroma, and inflammation in the pterygium head versus the body. IHC detection confirmed significantly lower AKT1, ATP5F1, and BAG3 expression in the head compared with the body(all P<0.05).
CONCLUSION:GEO-based bioinformatics and experiments confirmed that AKT1/ATP5F1/BAG3(mitochondrial genes)had significant differential expression in pterygium, correlating with pathological progression. They may regulate mitochondrial metabolism to mediate pterygium progression, offering new insights for targeted therapy.
[中图分类号]
[基金项目]
国家自然科学基金项目(No.81903879); 盐城市科技基础研究计划项目(No.YCBK202219); 江苏医药职业学院校地协同项目(No.20239418); 江苏医药职业学院科技创新团队(2024年度)