Chen Liyun, Ma Aiwei, Jiang Lewen, Fan Jufeng, Jiang Wenshi, Xu Mengjing, Bai Xujue, Zhou Jianda, Zhang Wancong, Tang Shijie
Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, China.
Plastic Surgery Institute of Shantou University Medical College, Shantou, Guangdong, China.
Protein Pept Lett. 2025;32(1):54-61. doi: 10.2174/0109298665308502240820115618.
This study aimed to identify novel proteins involved in retinoic acid (RA)-induced embryonic cleft palate development.
The palate tissues of the control and RA-treated E14.5 were dissected and subjected to iTRAQ-based proteomic analysis.
Differential expression analysis identified 196 significantly upregulated and 149 downregulated considerably proteins in RA-induced palate tissues. Comprehensive Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed the significant involvement of cytoplasmic translation, ribosome biogenesis, glycolysis/gluconeogenesis, and glutathione metabolism pathways in cleft palate pathogenesis triggered by RA. In particular, ribosome-related pathways were highly enriched, while glycolysis was disrupted. Protein-protein interaction analysis, facilitated by the STRING database, revealed a tightly interconnected network of differentially expressed proteins. Further analysis using the cytoHubba plugin in Cytoscape identified ten hub proteins, including Eif4a1, Gapdh, Eno1, Imp3, Rps20, Rps27a, Eef2, Hsp90ab1, Rpl19, and Rps16, indicating their potential roles in RA-induced cleft palate development, and thus positioning them as potential biomarkers for cleft palate.
These findings provide valuable insights into the proteomic changes associated with RA-induced cleft palate and shed light on key pathways and proteins that can contribute significantly to the pathogenesis of this congenital condition.
本研究旨在鉴定参与视黄酸（RA）诱导的胚胎腭裂发育的新蛋白质。
解剖对照和经RA处理的E14.5胚胎的腭组织，并进行基于iTRAQ的蛋白质组学分析。
差异表达分析确定了在RA诱导的腭组织中196种显著上调和149种显著下调的蛋白质。综合基因本体论和京都基因与基因组百科全书富集分析表明，细胞质翻译、核糖体生物发生、糖酵解/糖异生和谷胱甘肽代谢途径在RA引发的腭裂发病机制中显著参与。特别是，核糖体相关途径高度富集，而糖酵解被破坏。通过STRING数据库进行的蛋白质-蛋白质相互作用分析揭示了差异表达蛋白质的紧密互连网络。使用Cytoscape中的cytoHubba插件进行的进一步分析确定了十种枢纽蛋白，包括Eif4a1、Gapdh、Eno1、Imp3、Rps20、Rps27a、Eef2、Hsp90ab1、Rpl19和Rps16，表明它们在RA诱导的腭裂发育中的潜在作用，从而将它们定位为腭裂的潜在生物标志物。
这些发现为与RA诱导的腭裂相关的蛋白质组学变化提供了有价值的见解，并揭示了对这种先天性疾病发病机制有重大贡献的关键途径和蛋白质。
