Integrated analyses revealed the potential role and immune link of mitochondrial dysfunction between periodontitis and type 2 diabetes mellitus

作者全名：Pan, Shengyuan; Yang, Lanxin; Zhong, Wenjie; Wang, He; Lan, Yuyan; Chen, Qiyue; Yu, Simin; Yang, Fengze; Yan, Pingping; Peng, Houli; Liu, Xuan; Gao, Xiang; Song, Jinlin

作者地址：[Pan, Shengyuan; Yang, Lanxin; Zhong, Wenjie; Wang, He; Lan, Yuyan; Chen, Qiyue; Yu, Simin; Yang, Fengze; Yan, Pingping; Peng, Houli; Liu, Xuan; Gao, Xiang; Song, Jinlin] Chongqing Med Univ, Coll Stomatol, Chongqing 401147, Peoples R China; [Pan, Shengyuan; Yang, Lanxin; Zhong, Wenjie; Wang, He; Lan, Yuyan; Chen, Qiyue; Yu, Simin; Yang, Fengze; Yan, Pingping; Peng, Houli; Liu, Xuan; Gao, Xiang; Song, Jinlin] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing 401147, Peoples R China; [Pan, Shengyuan; Yang, Lanxin; Zhong, Wenjie; Wang, He; Lan, Yuyan; Chen, Qiyue; Yu, Simin; Yang, Fengze; Yan, Pingping; Peng, Houli; Liu, Xuan; Gao, Xiang; Song, Jinlin] Chongqing Municipal Key Lab Oral Biomed Engn High, Chongqing 401147, Peoples R China

通信作者：Gao, X; Song, JL (通讯作者)，Chongqing Med Univ, Coll Stomatol, Chongqing 401147, Peoples R China.

来源：INTERNATIONAL IMMUNOPHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001217661900001

JCR分区：Q1

影响因子：4.8

年份：2024

卷号：130

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Periodontitis; T2DM; Mitochondrial dysfunction; Immune landscape; Bioinformatics analysis

摘要：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 immunerelated 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 immunoinflammatory pathways. In total, 116 MDDEGs, eight hub MDDEGs, and two biomarkers were identified. qRTPCR 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.

基金机构：National Natural Science Foundation of China [U22A20314, 82071093, 31700850]; National Key R & D of Program of China [2022YFC2504200]; Program for Youth Innovation in Future Medicine of Chongqing Medical University [W0055]; Chongqing Young and Middle-aged Medical High-end Talent Studio

基金资助正文：<B>Acknowledgments</B> S. P. and L. Y. contributed equally to this work and shared the first authorship. This work was supported by National Natural Science Foundation of China (U22A20314, 82071093, 31700850) , National Key R & D of Program of China (Grant No. 2022YFC2504200) , Program for Youth Innovation in Future Medicine of Chongqing Medical University (W0055) , and Chongqing Young and Middle-aged Medical High-end Talent Studio. The authors sincerely acknowledge the doctors who of-fering great assistance in supplying dataset. The authors also sincerely thank the editors and reviewers for their valuable advice.