Background. Nifedipine-induced gingival overgrowth (NGO) is a multifactorial pathogenesis with increased extracellular matrix including collagen and glycans, inflammatory cytokines, and phenotype changes of fibroblasts. However, the molecular etiology of NGO is not well understood. The objective of this study is to investigate the key genes in the pathogenesis of NGO. Methods. In this study, we examined the proliferation and migration abilities of fibroblasts derived from patients with chronic periodontitis, nifedipine nonresponder gingival overgrowth, gingival overgrowth caused by nifedipine, and healthy normal gingiva. We conducted RNA-Seq on these four groups of fibroblasts and analysed the differentially expressed genes (DEGs). Results. Fibroblasts derived from NGO patients had higher proliferation and migration abilities than those of the other groups. Protein-protein interaction network analysis indicated that TGFB2, ITGA8, ITGA11, FGF5, PLA2G4D, PLA2G2F, PTGS1, CSF1, LPAR1, CCL3, and NKX3-1 are involved in the development of NGO. These factors are related to the arachidonic acid metabolism and PI3K/AKT signaling pathways. Conclusion. Transcriptional gene expression analysis identified a number of DEGs that might be functionally related to gingival overgrowth induced by nifedipine. Our study provides important information on the molecular mechanism underlying nifedipine-induced gingival overgrowth.

中文翻译：

---

转录分析揭示了硝苯地平引起的牙龈过度生长发病机制中的关键基因。


背景。硝苯地平诱导的牙龈过度生长 (NGO) 是一种多因素发病机制，包括胶原蛋白和聚糖、炎症细胞因子和成纤维细胞表型变化等细胞外基质增加。然而，NGO 的分子病因学尚不清楚。本研究的目的是探讨NGO发病机制中的关键基因。方法。在本研究中，我们检测了慢性牙周炎患者、硝苯地平无反应者牙龈过度生长、硝苯地平引起的牙龈过度生长以及健康正常牙龈患者来源的成纤维细胞的增殖和迁移能力。我们对这四组成纤维细胞进行了RNA-Seq，并分析了差异表达基因（DEG）。结果。来自NGO患者的成纤维细胞比其他组的成纤维细胞具有更高的增殖和迁移能力。蛋白质-蛋白质相互作用网络分析表明TGFB2、ITGA8、ITGA11、FGF5、PLA2G4D、PLA2G2F、PTGS1、CSF1、LPAR1、CCL3和NKX3-1参与NGO的发育。这些因素与花生四烯酸代谢和PI3K/AKT信号通路有关。结论。转录基因表达分析确定了许多可能与硝苯地平诱导的牙龈过度生长在功能上相关的DEG。我们的研究提供了有关硝苯地平诱导牙龈过度生长的分子机制的重要信息。