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Glycin-proline-hydroxyproline Modified N-terminal 20 Peptide from CEMP1 Blocks Calcium Ion Influx to Alleviate Inflammatory Response in Gingival Fibroblasts
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DOI:10.1016/j.ejphar.2026.178948.png)
Abstract
En 中文
Gingival fibroblasts play a pivotal role in the progression of periodontitis, and targeted inhibition of calcium ion influx in gingival fibroblasts represents a potential therapeutic strategy for ameliorating periodontal inflammation. The N-terminal 20-amino-acid peptide derived from cementum protein 1 (N20) possesses calcium-chelating capacity, whereas the glycine-proline-hydroxyproline (GPH) tripeptide confers collagen-targeting binding ability. In this study, we engineered a GPH-modified N20 peptide (GPH-N20) and systematically investigated its anti-inflammatory effects in vitro. Our results demonstrated that GPH-N20 achieved high-efficiency targeted binding to both normal gingival fibroblasts and lipopolysaccharide (LPS)-stimulated inflammatory macrophages. This specific binding significantly blocked intracellular calcium influx and aberrant calcium signaling activation, and effectively abrogated LPS-induced pro-inflammatory responses in these cells. Mechanistic analyses further revealed that the dual functions of GPH-N20, its collagen-targeting capacity and calcium-chelating activity, synergistically suppressed the activation of the LPS-triggered Ca2+/calmodulin-dependent protein kinase II / nuclear factor-κB (CaMKII/NF-κB) signaling pathway, thereby attenuating the downstream pro-inflammatory cascades. Collectively, these findings validate that GPH-N20 is a promising anti-inflammatory agent with specific efficacy in alleviating gingival tissue inflammation, and thus provides a novel therapeutic candidate for the clinical management of periodontal inflammatory diseases.
Keywords:
GPH-N20 peptide
gingival fibroblasts
calcium ion influx
periodontitis
anti-inflammatory response
Journal
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4.7
Papers:
2.3W
Citations:
4.0W
