Abstract
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.
Highlights
Drug-induced gingival overgrowth (DIGO)/hyperplasia is a frequent adverse effect observed in patients treated with anticonvulsant, immunosuppressant, and some antihypertensive medications [1,2,3]
Based on PPI network analysis, we discovered several significant differentially expressed genes (DEGs) that may participate in the regulation of Nifedipine-induced gingival overgrowth (NGO), such as TGFB2, ITGA8, ITGA11, FGF5, PLA2G4D, PLA2G2F, PTGS1, CSF1, LPAR1, CCL3, and NKX3-1 (Figure 4(b))
The pathogenic mechanisms of DIGO are known to be genetically predetermined, as gingival fibroblasts are more sensitive to Gene Ontology (GO)-inducing drug than other fibroblast subpopulations
Summary
Drug-induced gingival overgrowth (DIGO)/hyperplasia is a frequent adverse effect observed in patients treated with anticonvulsant, immunosuppressant, and some antihypertensive medications [1,2,3]. Several factors are thought to influence the relationship between nifedipine and gingival overgrowth, including local inflammation, drug-induced alterations in gingival connective tissue homeostasis, and genetic predisposition [7, 8]. NGO is characterized by cell proliferation and extracellular matrix (ECM) component accumulation in gingival connective tissues Inflammatory cytokines, such as interleukin-1β [9] and interleukin-6 [10], have been reported to synergistically enhance proliferation and collagen production in human gingival fibroblasts (hGFs) [11]. Nifedipine-induced gingival overgrowth (NGO) is a multifactorial pathogenesis with increased extracellular matrix including collagen and glycans, inflammatory cytokines, and phenotype changes of fibroblasts. 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. Our study provides important information on the molecular mechanism underlying nifedipine-induced gingival overgrowth
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