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Updated: Jun 6, 2026
A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites
Published on: August 8, 2014
USP22 knockdown attenuates P. gingivalis-induced EndoMT and CNS inflammation: a link between periodontitis and
Hui Wang1, Mengxian Wang2, Jiaming Shen3
1Department of Stomatology, Nantong First People's Hospital, Southeast University Affiliated Nantong First People's Hospital, Nantong, China.
Objective:
Chronic periodontitis is a significant risk factor for systemic disorders. However, the precise mechanism through which the "oral-brain axis" mediates its impact on the central nervous system remains unclear. This study aimed to investigate whether the periodontal pathogen Porphyromonas gingivalis (P. gingivalis) induces endothelial-mesenchymal transition (EndoMT), thereby disrupting the blood-brain barrier (BBB) and triggering neuroinflammation, and to elucidate the regulatory role of the deubiquitinating enzyme USP22 in this process.
Methods:
A chronic oral infection model of P. gingivalis was established in mice, which was confirmed by assessing inflammatory factor levels in periodontal tissues. Endothelial tight junction proteins (ZO-1 and Claudin-5), a mesenchymal marker (α-SMA), and inflammatory mediators (iNOS) were detected by Western blotting. IL-1β and IL-6 mRNA levels were detected by quantitative real-time PCR. Human brain microvascular endothelial cells (HBMECs) were stimulated with P. gingivalis-derived lipopolysaccharide (LPS) to mimic inflammation in vitro. Endothelial-specific knockdown of USP22 in the hippocampus was achieved via adeno-associated virus (AAV) delivery to validate its role in vivo. STRING bioinformatics tool to investigate its potential downstream pathways.
Results:
Oral infection with P. gingivalis successfully induced periodontitis in mice and led to EndoMT in the hippocampus, characterized by downregulation of ZO-1 and Claudin-5 and upregulation of α-SMA, along with inflammatory activation evidenced by elevated levels of iNOS, IL-1β mRNA, and IL-6 mRNA. USP22 expression was significantly upregulated both in hippocampal tissues of P. gingivalis-infected mice and in LPS-exposed HBMECs. Knockdown of USP22 attenuated LPS-induced EndoMT and suppressed the expression of inflammatory markers in HBMECs. Similarly, endothelial-specific knockdown of USP22 mitigated P. gingivalis-induced EndoMT and hippocampal inflammation in vivo.
Conclusion:
These findings demonstrate that P. gingivalis promotes EndoMT and neuroinflammation in the hippocampus. Endothelial-specific inhibition of USP22 alleviates BBB dysfunction and central inflammatory responses, highlighting USP22 as a potential therapeutic target for neuroinflammatory disorders associated with chronic periodontitis.
