Porphyromonas gingivalis msRNA P.G_45033 induces amyloid-β production by enhancing glycolysis and histone lactylation in macrophages

Yonghuan Zhang; Yangyang Sun; Ying Hu; Shaowen Zheng; Haigang Shao; Li Lin; Yaping Pan; Chen Li

doi:10.1016/j.intimp.2023.110468

Porphyromonas gingivalis msRNA P.G_45033 induces amyloid-β production by enhancing glycolysis and histone lactylation in macrophages

Int Immunopharmacol. 2023 Aug:121:110468. doi: 10.1016/j.intimp.2023.110468. Epub 2023 Jun 13.

Authors

Yonghuan Zhang¹, Yangyang Sun¹, Ying Hu¹, Shaowen Zheng¹, Haigang Shao¹, Li Lin¹, Yaping Pan², Chen Li³

Affiliations

¹ Department of Periodontology, School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, China; Liaoning Provincial Key Laboratory of Oral Disease, Shenyang, Liaoning, China.
² Department of Periodontology, School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, China; Liaoning Provincial Key Laboratory of Oral Disease, Shenyang, Liaoning, China. Electronic address: yppan@cmu.edu.cn.
³ Department of Periodontology, School and Hospital of Stomatology, China Medical University, Shenyang, Liaoning, China; Liaoning Provincial Key Laboratory of Oral Disease, Shenyang, Liaoning, China. Electronic address: lichen@cmu.edu.cn.

PMID: 37320870
DOI: 10.1016/j.intimp.2023.110468

Abstract

Background: High expression of amyloid-β (Aβ) in periodontal tissue could contribute to exacerbating the development of both periodontitis and Alzheimer's disease (AD). Porphyromonas gingivalis (P. gingivalis) as a periodontal pathogen expresses msRNAs, which can regulate gene transcription in host cells.

Objective: The aim of this study is to reveal the mechanism of msRNA P.G_45033, a high copy msRNA in P. gingivalis, inducing Aβ expression in macrophages, and provide a new insight to explain the development of periodontitis, and also to explain the role of periodontal infection on AD.

Methods: The levels of glucose consumption, pyruvate and lactate productions in macrophages after transfection with msRNA P.G_45033 were detected. Miranda, TargetScan, and RNAhybrid databases were used to predict the target gene of msRNA P.G_45033, and GO analysis was conducted to describe the functions of the overlapping ones. RT² glucose-metabolism PCR Array was used to verify the relationship between msRNA P.G_45033 and the expression of genes related to glucose metabolism. The levels of histone Kla were detected using western blotting. The levels of Aβ in the macrophages and the culture medium were detected by immunofluorescence and ELISA, respectively.

Results: The levels of glucose consumption, pyruvate and lactate productions were increased after transfection of msRNA P.G_45033 in macrophages. GO analysis revealed that target genes were enriched in the metabolic process. RT² glucose-metabolism PCR Array showed the expression of genes associated with glycolysis. The results of western blotting showed that the level of histone Kla was increased in macrophages. The results of immunofluorescence and ELISA showed that Aβ levels in macrophages and culture medium were increased after transfection.

Conclusion: The present study revealed that msRNA P.G_45033 can induce Aβ production by enhancing glycolysis and histone Kla in macrophages.

Keywords: Alzheimer's disease; Glycolysis; Histone; Periodontitis.

MeSH terms

Alzheimer Disease* / metabolism
Amyloid beta-Peptides / metabolism
Glucose / metabolism
Glycolysis
Histones / metabolism
Humans
Lactates
Macrophages / metabolism
Periodontitis* / metabolism
Porphyromonas gingivalis
Pyruvates

Substances

Histones
Amyloid beta-Peptides
Lactates
Pyruvates
Glucose