Integrated analyses revealed the potential role and immune link of mitochondrial dysfunction between periodontitis and type 2 diabetes mellitus.
Int Immunopharmacol
; 130: 111796, 2024 Mar 30.
Article
em En
| MEDLINE
| ID: mdl-38452412
ABSTRACT
There is a reciprocal comorbid relationship between periodontitis and type 2 diabetes mellitus (T2DM). Recent studies have suggested that mitochondrial dysfunction (MD) could be the key driver underlying this comorbidity. The aim of this study is to provide novel understandings into the potential molecular mechanisms between MD and the comorbidity, and identify potential therapeutic targets for personalized clinical management. MD-related differentially expressed genes (MDDEGs) were identified. Enrichment analyses and PPI network analysis were then conducted. Six algorithms were used to explore the hub MDDEGs, and these were validated by ROC analysis and qRT-PCR. Co-expression and potential drug targeting analyses were then performed. Potential biomarkers were identified using LASSO regression. The immunocyte infiltration levels in periodontitis and T2DM were evaluated via CIBERSORTx and validated in mouse models. Subsequently, MD-related immune-related genes (MDIRGs) were screened by WGCNA. The in vitro experiment verified that MD was closely associated with this comorbidity. GO and KEGG analyses demonstrated that the connection between periodontitis and T2DM was mainly enriched in immuno-inflammatory pathways. In total, 116 MDDEGs, eight hub MDDEGs, and two biomarkers were identified. qRT-PCR revealed a distinct hub MDDEG expression pattern in the comorbidity group. Altered immunocytes in disease samples were identified, and their correlations were explored. The in vivo examination revealed higher infiltration levels of inflammatory immunocytes. The findings of this study provide insight into the mechanism underlying the gene-mitochondria-immunocyte network and provide a novel reference for future research into the function of mitochondria in periodontitis and T2DM.
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Bases de dados:
MEDLINE
Assunto principal:
Periodontite
/
Doenças Mitocondriais
/
Diabetes Mellitus Tipo 2
Limite:
Animals
Idioma:
En
Revista:
Int Immunopharmacol
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Ano de publicação:
2024
Tipo de documento:
Article