Porphyromonas gingivalis bacteremia increases the permeability of the blood-brain barrier via the Mfsd2a/Caveolin-1 mediated transcytosis pathway.
10.1038/s41368-022-00215-y
- Author:
Shuang LEI
1
;
Jian LI
2
;
Jingjun YU
1
;
Fulong LI
1
;
Yaping PAN
1
;
Xu CHEN
3
;
Chunliang MA
1
;
Weidong ZHAO
4
;
Xiaolin TANG
5
Author Information
1. Department of Periodontics, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Disease, China Medical University, No. 117, Nanjing North Street, Heping District, Shenyang, China.
2. Department of Preventive Dentistry, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Disease, China Medical University, Shenyang, China.
3. Department of Pediatric Dentistry, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Disease, China Medical University, No. 117, Nanjing North Street, Heping District, Shenyang, China.
4. Department of Developmental Cell Biology, Key Laboratory of Cell Biology, China Medical University, 77 Puhe Road, Shenbei New District, Shenyang, China.
5. Department of Periodontics, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Disease, China Medical University, No. 117, Nanjing North Street, Heping District, Shenyang, China. xltang@cmu.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Animals;
Rats;
Bacteremia/metabolism*;
Blood-Brain Barrier/microbiology*;
Caveolin 1/metabolism*;
Gingipain Cysteine Endopeptidases/metabolism*;
Permeability;
Porphyromonas gingivalis/pathogenicity*;
Transcytosis;
Virulence Factors/metabolism*
- From:
International Journal of Oral Science
2023;15(1):3-3
- CountryChina
- Language:English
-
Abstract:
Bacteremia induced by periodontal infection is an important factor for periodontitis to threaten general health. P. gingivalis DNA/virulence factors have been found in the brain tissues from patients with Alzheimer's disease (AD). The blood-brain barrier (BBB) is essential for keeping toxic substances from entering brain tissues. However, the effect of P. gingivalis bacteremia on BBB permeability and its underlying mechanism remains unclear. In the present study, rats were injected by tail vein with P. gingivalis three times a week for eight weeks to induce bacteremia. An in vitro BBB model infected with P. gingivalis was also established. We found that the infiltration of Evans blue dye and Albumin protein deposition in the rat brain tissues were increased in the rat brain tissues with P. gingivalis bacteremia and P. gingivalis could pass through the in vitro BBB model. Caveolae were detected after P. gingivalis infection in BMECs both in vivo and in vitro. Caveolin-1 (Cav-1) expression was enhanced after P. gingivalis infection. Downregulation of Cav-1 rescued P. gingivalis-enhanced BMECs permeability. We further found P. gingivalis-gingipain could be colocalized with Cav-1 and the strong hydrogen bonding between Cav-1 and arg-specific-gingipain (RgpA) were detected. Moreover, P. gingivalis significantly inhibited the major facilitator superfamily domain containing 2a (Mfsd2a) expression. Mfsd2a overexpression reversed P. gingivalis-increased BMECs permeability and Cav-1 expression. These results revealed that Mfsd2a/Cav-1 mediated transcytosis is a key pathway governing BBB BMECs permeability induced by P. gingivalis, which may contribute to P. gingivalis/virulence factors entrance and the subsequent neurological impairments.
