Identification of cross-talk pathways and ferroptosis-related genes in periodontitis and type 2 diabetes mellitus by bioinformatics analysis and experimental validation
PurposeThere is a bidirectional relationship between periodontitis and type 2 diabetes mellitus (T2DM). The aim of this study was to further explore the pathogenesis of this comorbidity, screen out ferroptosis-related genes involved in the pathological process, and predict potential drug targets to...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2022-09-01
|
Series: | Frontiers in Immunology |
Subjects: | |
Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1015491/full |
_version_ | 1811208431915237376 |
---|---|
author | Shengyuan Pan Shengyuan Pan Shengyuan Pan Bo Hu Bo Hu Bo Hu Jicheng Sun Jicheng Sun Jicheng Sun Zun Yang Zun Yang Zun Yang Wenliang Yu Wenliang Yu Wenliang Yu Zangmin He Zangmin He Zangmin He Xiang Gao Xiang Gao Xiang Gao Jinlin Song Jinlin Song Jinlin Song |
author_facet | Shengyuan Pan Shengyuan Pan Shengyuan Pan Bo Hu Bo Hu Bo Hu Jicheng Sun Jicheng Sun Jicheng Sun Zun Yang Zun Yang Zun Yang Wenliang Yu Wenliang Yu Wenliang Yu Zangmin He Zangmin He Zangmin He Xiang Gao Xiang Gao Xiang Gao Jinlin Song Jinlin Song Jinlin Song |
author_sort | Shengyuan Pan |
collection | DOAJ |
description | PurposeThere is a bidirectional relationship between periodontitis and type 2 diabetes mellitus (T2DM). The aim of this study was to further explore the pathogenesis of this comorbidity, screen out ferroptosis-related genes involved in the pathological process, and predict potential drug targets to develop new therapeutic strategies.MethodsCommon cross-talk genes were identified from periodontitis datasets (GSE16134, GSE10334 and GSE106090) and T2DM databases (DisGeNET and GeneCard). Then, GO and KEGG enrichment analyses, PPI network analysis and hub gene identification were performed. The association between ferroptosis and periodontitis with T2DM was investigated by Pearson correlation analysis. Core ferroptosis-related cross-talk genes were identified and verified by qRT-PCR. Potential drugs targeting these core genes were predicted via DGIDB.ResultsIn total, 67 cross-talk genes and two main signalling pathways (immuno-inflammatory pathway and AGE-RAGE signalling pathway) were identified. Pearson correlation analysis indicated that ferroptosis served as a crucial target in the pathological mechanism and treatment of periodontitis with T2DM. IL-1β, IL-6, NFE2L2 and ALOX5 were identified as core ferroptosis-related genes and the qRT-PCR detection results were statistically different. In total, 13 potential drugs were screened out, among which, Echinacea and Ibudilast should be developed first.ConclusionsThis study contributes to a deeper understanding of the common pathogenesis of periodontitis and T2DM and provides new insights into the role of ferroptosis in this comorbidity. In addition, two drugs with potential clinical application value were identified. The potential utility of these drugs requires further experimental investigation. |
first_indexed | 2024-04-12T04:21:07Z |
format | Article |
id | doaj.art-69c20b3f10fa4f2d9c2c4b35eeaeb59e |
institution | Directory Open Access Journal |
issn | 1664-3224 |
language | English |
last_indexed | 2024-04-12T04:21:07Z |
publishDate | 2022-09-01 |
publisher | Frontiers Media S.A. |
record_format | Article |
series | Frontiers in Immunology |
spelling | doaj.art-69c20b3f10fa4f2d9c2c4b35eeaeb59e2022-12-22T03:48:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.10154911015491Identification of cross-talk pathways and ferroptosis-related genes in periodontitis and type 2 diabetes mellitus by bioinformatics analysis and experimental validationShengyuan Pan0Shengyuan Pan1Shengyuan Pan2Bo Hu3Bo Hu4Bo Hu5Jicheng Sun6Jicheng Sun7Jicheng Sun8Zun Yang9Zun Yang10Zun Yang11Wenliang Yu12Wenliang Yu13Wenliang Yu14Zangmin He15Zangmin He16Zangmin He17Xiang Gao18Xiang Gao19Xiang Gao20Jinlin Song21Jinlin Song22Jinlin Song23College of Stomatology, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, ChinaChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, ChinaChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, ChinaChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, ChinaChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, ChinaChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, ChinaChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, ChinaChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, ChinaCollege of Stomatology, Chongqing Medical University, Chongqing, ChinaChongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, ChinaChongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, ChinaPurposeThere is a bidirectional relationship between periodontitis and type 2 diabetes mellitus (T2DM). The aim of this study was to further explore the pathogenesis of this comorbidity, screen out ferroptosis-related genes involved in the pathological process, and predict potential drug targets to develop new therapeutic strategies.MethodsCommon cross-talk genes were identified from periodontitis datasets (GSE16134, GSE10334 and GSE106090) and T2DM databases (DisGeNET and GeneCard). Then, GO and KEGG enrichment analyses, PPI network analysis and hub gene identification were performed. The association between ferroptosis and periodontitis with T2DM was investigated by Pearson correlation analysis. Core ferroptosis-related cross-talk genes were identified and verified by qRT-PCR. Potential drugs targeting these core genes were predicted via DGIDB.ResultsIn total, 67 cross-talk genes and two main signalling pathways (immuno-inflammatory pathway and AGE-RAGE signalling pathway) were identified. Pearson correlation analysis indicated that ferroptosis served as a crucial target in the pathological mechanism and treatment of periodontitis with T2DM. IL-1β, IL-6, NFE2L2 and ALOX5 were identified as core ferroptosis-related genes and the qRT-PCR detection results were statistically different. In total, 13 potential drugs were screened out, among which, Echinacea and Ibudilast should be developed first.ConclusionsThis study contributes to a deeper understanding of the common pathogenesis of periodontitis and T2DM and provides new insights into the role of ferroptosis in this comorbidity. In addition, two drugs with potential clinical application value were identified. The potential utility of these drugs requires further experimental investigation.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1015491/fullferroptosisdrug predictionperiodontitistype 2 diabetes mellituspathway |
spellingShingle | Shengyuan Pan Shengyuan Pan Shengyuan Pan Bo Hu Bo Hu Bo Hu Jicheng Sun Jicheng Sun Jicheng Sun Zun Yang Zun Yang Zun Yang Wenliang Yu Wenliang Yu Wenliang Yu Zangmin He Zangmin He Zangmin He Xiang Gao Xiang Gao Xiang Gao Jinlin Song Jinlin Song Jinlin Song Identification of cross-talk pathways and ferroptosis-related genes in periodontitis and type 2 diabetes mellitus by bioinformatics analysis and experimental validation Frontiers in Immunology ferroptosis drug prediction periodontitis type 2 diabetes mellitus pathway |
title | Identification of cross-talk pathways and ferroptosis-related genes in periodontitis and type 2 diabetes mellitus by bioinformatics analysis and experimental validation |
title_full | Identification of cross-talk pathways and ferroptosis-related genes in periodontitis and type 2 diabetes mellitus by bioinformatics analysis and experimental validation |
title_fullStr | Identification of cross-talk pathways and ferroptosis-related genes in periodontitis and type 2 diabetes mellitus by bioinformatics analysis and experimental validation |
title_full_unstemmed | Identification of cross-talk pathways and ferroptosis-related genes in periodontitis and type 2 diabetes mellitus by bioinformatics analysis and experimental validation |
title_short | Identification of cross-talk pathways and ferroptosis-related genes in periodontitis and type 2 diabetes mellitus by bioinformatics analysis and experimental validation |
title_sort | identification of cross talk pathways and ferroptosis related genes in periodontitis and type 2 diabetes mellitus by bioinformatics analysis and experimental validation |
topic | ferroptosis drug prediction periodontitis type 2 diabetes mellitus pathway |
url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1015491/full |
work_keys_str_mv | AT shengyuanpan identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT shengyuanpan identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT shengyuanpan identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT bohu identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT bohu identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT bohu identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT jichengsun identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT jichengsun identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT jichengsun identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT zunyang identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT zunyang identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT zunyang identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT wenliangyu identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT wenliangyu identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT wenliangyu identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT zangminhe identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT zangminhe identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT zangminhe identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT xianggao identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT xianggao identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT xianggao identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT jinlinsong identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT jinlinsong identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation AT jinlinsong identificationofcrosstalkpathwaysandferroptosisrelatedgenesinperiodontitisandtype2diabetesmellitusbybioinformaticsanalysisandexperimentalvalidation |