UBC Theses and Dissertations
Suppression of alpha v beta 6 integrin in gingival epithelium in periodontal diseases Bi, Jiarui
Globally, about half of the adult population suffers from periodontal diseases. In periodontal diseases, multispecies bacterial biofilms accumulate between the epithelium of gingiva and teeth resulting in inflammation, periodontal pocket formation and alveolar bone loss. Integrin αvβ6 maintains anti-inflammatory transforming growth factor-β1 (TGF-β1) signaling in healthy junctional epithelium. However, it is significantly reduced in the pocket epithelium in periodontal disease. In this study, we show that β6 integrin mRNA and protein expression is suppressed by bacterial biofilms in cultured gingival epithelial cells (GECs). We found that biofilm-induced suppression of β6 integrin expression is driven by autocrine epidermal growth factor receptor (EGFR) signaling and attenuation of TGF-β1 signaling which leads to enhanced pro-inflammatory response. The biofilm-initiated β6 integrin downregulation in GEC can be prevented by blocking EGFR signaling. In addition, selective EGFR inhibitors significantly reduce periodontal inflammation and bone loss in an experimental periodontitis model in vivo. Therefore, blocking EGFR signaling could serve as a novel approach to reduce inflammation and bone loss in periodontal disease.
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