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SIRT6 alleviates senescence induced by Porphyromonas gingivalis in human gingival fibroblasts.
- Source :
-
Molecular biology reports [Mol Biol Rep] 2024 Sep 11; Vol. 51 (1), pp. 976. Date of Electronic Publication: 2024 Sep 11. - Publication Year :
- 2024
-
Abstract
- Objective: Bidirectional influences between senescence and inflammation are newly discovered. This study aimed to clarify the roles and mechanism of Porphyromonas gingivalis (P. gingivalis) in exacerbating senescence in human gingival fibroblasts (HGFs).<br />Design: Subgingival plaque and gingivae were collected from twenty-four periodontitis patients and eighteen periodontally healthy subjects. Quantities of P. gingivalis in subgingival plaque were explored using real-time PCR and the expressions of p53, p21 and SIRT6 in gingivae were detected by IHC. Moreover, senescence in HGFs was induced by P. gingivalis lipopolysaccharide (LPS) and the expressions of senescence-related β-galactosidase (SA-β-gal), p53, p21 and senescence-associated secretory phenotype (IL-6 and IL-8) with or without treatment by SIRT6 activator UBCS039 were explored by IHC, western blot and ELISA, respectively. In addition, the levels of SIRT6, Nrf2, HO-1 and reactive oxygen species (ROS) were examined by western blot and flow cytometry.<br />Results: Quantities of P. gingivalis in subgingival plaque and semi-quantitative scores of p53 and p21 in gingivae of periodontitis patients were increased compared with healthy controls (p < 0.05), while SIRT6 score in periodontitis patients was decreased (p < 0.001). Quantities of P. gingivalis were positively correlated with p53 and p21 scores (0.6 < r < 0.9, p < 0.01), and negatively correlated with SIRT6 score (-0.9 < r<-0.6, p < 0.01). Moreover, P. gingivalis LPS increased the levels of SA-β-gal, p53, p21, IL-6, IL-8 and ROS and decreased the levels of SIRT6, Nrf2 and HO-1 in HGFs, which was rescued by UBCS039 (p < 0.05).<br />Conclusions: P. gingivalis LPS could induce senescence of HGFs, which could be reversed by SIRT6 via Nrf2-HO-1 signaling pathway.<br /> (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
- Subjects :
- Humans
Male
Female
Adult
Lipopolysaccharides pharmacology
Periodontitis microbiology
Periodontitis metabolism
Tumor Suppressor Protein p53 metabolism
Middle Aged
Heme Oxygenase-1 metabolism
Heme Oxygenase-1 genetics
Interleukin-6 metabolism
Interleukin-8 metabolism
Cyclin-Dependent Kinase Inhibitor p21 metabolism
Cyclin-Dependent Kinase Inhibitor p21 genetics
Porphyromonas gingivalis pathogenicity
Gingiva microbiology
Gingiva metabolism
Fibroblasts metabolism
Sirtuins metabolism
Sirtuins genetics
Cellular Senescence
NF-E2-Related Factor 2 metabolism
NF-E2-Related Factor 2 genetics
Reactive Oxygen Species metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4978
- Volume :
- 51
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular biology reports
- Publication Type :
- Academic Journal
- Accession number :
- 39259343
- Full Text :
- https://doi.org/10.1007/s11033-024-09913-8