Abstract
Background
Hyperglycemic micro‐environment induced by diabetes could regulate the response of periodontal tissues to pathogenic microorganisms in which disruption of autophagy lysosomal pathway (ALP) may participate. This study aimed to explore the mechanisms underlying how high glucose regulates ALP in gingival epithelial cells (GECs).
Methods
Human gingival tissues in healthy group(C), periodontitis group(P), diabetes group (DM) and diabetes+periodontitis group (DP) were collected and were applied to observe the fusion of autophagy and lysosome. Diabetic mouse model with periodontitis was established and RNA‐seq was applied to investigate the expression of ALP‐associated genes in gingival epithelium. To explore the key role of ATP6V0C in the disruption of ALP by high glucose, human gingival epithelial cells (HGECs) were cultured in 5.5mM/25mM glucose medium for 48h and followed by Porphyromonas gingivalis(Pg) stimulation for 0h/6h/12h. HBLV‐h‐ATP6V0C was transfected in HGECs which were stimulated by 25mM high glucose condition.
Results
Immunofluorescence double staining exhibited the disruption of ALP in human gingival epithelium in diabetes groups and HGECs under 25mM glucose condition, accompanied with significantly down‐regulated lysosomal acidity. RNA‐seq of mouse gingival epithelium screened out Atp6v0c. Compared with HGECs in normal culture medium, ATP6V0C expression and LC3‐II/I expression ratio were significantly down‐regulated, with an up‐regulated expression of P62, IL1β in HGECs under high glucose condition. Over‐expression of ATP6V0C rescued high glucose induced disruption of ALP in HBLV‐h‐ATP6V0C transfected HGECs, with significantly up‐regulation of LC3‐II/I and down‐regulation of P62, IL1β.
Conclusion
ATP6V0C mediates high glucose‐induced ALP disruption in HGECs, eventually exacerbates periodontal inflammation.
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https://aap.onlinelibrary.wiley.com/doi/abs/10.1002/JPER.19-0262?af=R
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