Gingipain and oncostatin M synergistically disrupt kidney tight junctions in periodontitis-associated acute kidney injury.

Publisher: American Academy of Periodontology Country of Publication: United States NLM ID: 8000345 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1943-3670 (Electronic) Linking ISSN: 00223492 NLM ISO Abbreviation: J Periodontol Subsets: MEDLINE

Original Publication: [Chicago] American Academy of Periodontology.

Acute Kidney Injury*/metabolism ; Acute Kidney Injury*/etiology ; Bacteroidaceae Infections*/complications ; Gingipain Cysteine Endopeptidases*/metabolism ; Oncostatin M*/metabolism ; Periodontitis*/complications ; Periodontitis*/microbiology ; Porphyromonas gingivalis*/physiology; Animals ; Humans ; Male ; Mice ; Disease Models, Animal ; Kidney ; Mice, Inbred C57BL ; Reperfusion Injury/complications ; Tight Junctions/metabolism

Background: Acute kidney injury (AKI) is characterized by rapid renal decline. Periodontitis, a chronic oral inflammatory disease, is increasingly associated with renal dysfunction. Although periodontitis is recognized as a contributor to kidney damage, the mechanisms linking it to AKI remain unclear.
Methods: This study explored the effects of Porphyromonas gingivalis (P. gingivalis) W83-infected periodontitis on AKI in C57BL/6J mice, using ischemia-reperfusion injury 55 days post-infection. Gingipain inhibitors, KYT-1 and KYT-36, were applied. Detection of P. gingivalis was performed using quantitative real-time polymerase chain reaction (qRT-PCR) and PCR, while transcriptome sequencing, qRT-PCR, immunohistochemistry, and immunofluorescence staining assessed renal damage. In vitro, HK-2 cells were exposed to P. gingivalis at a multiplicity of infection of 10 for 48 h, with inhibition by gingipain or oncostatin M (OSM). Disruption of tight junctions (TJs) was quantified using qRT-PCR, transepithelial electrical resistance, and cell counting kit-8 assays.
Results: Periodontitis worsened AKI, linked to P. gingivalis infection and renal TJ disruption in the kidney. P. gingivalis infection activated OSM expression, which correlated positively with gingipain. Significantly, OSM and gingipain might collaboratively contribute to the damage of renal TJs, with the reduced expression of TJ proteins. Suppressing gingipain activity presented itself as a protective strategy against the destruction of TJs and the attendant worsening of AKI due to periodontitis.
Conclusions: Our study enhances the understanding of the interplay between periodontitis and AKI, highlighting the harmful impact of P. gingivalis in AKI.
(© 2024 American Academy of Periodontology.)

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YSP202314 the Young Scientist Program of Beijing Stomatological Hospital, Capital Medical University; 2020-3-49 the Second Batch of Science and Technology Plan Projects of Jinan Municipal Health Commission; 2023-2-161 the Second Batch of Science and Technology Plan Projects of Jinan Municipal Health Commission; 2021-01 the Dean's Research Fund of Jinan Stomatological Hospital; 202328023 the Jinan Clinical Medical Science and Technology Innovation Plan Project; YSP202314 The Young Scientist Program of Beijing Stomatological Hospital, Capital Medical University

Keywords: Porphyromonas gingivalis; acute kidney injury; gingipain cysteine endopeptidases; oncostatin M; periodontitis; tight junctions

0 (Gingipain Cysteine Endopeptidases)
106956-32-5 (Oncostatin M)

Date Created: 20240704 Date Completed: 20240930 Latest Revision: 20241015

20250114

10.1002/JPER.24-0007

38963713