Identification of cross-talk pathways and ferroptosis-related genes in periodontitis and type 2 diabetes mellitus by bioinformatics analysis and experimental validation

作者全名："Pan, Shengyuan; Hu, Bo; Sun, Jicheng; Yang, Zun; Yu, Wenliang; He, Zangmin; Gao, Xiang; Song, Jinlin"

作者地址："[Pan, Shengyuan; Hu, Bo; Sun, Jicheng; Yang, Zun; Yu, Wenliang; He, Zangmin; Gao, Xiang; Song, Jinlin] Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China; [Pan, Shengyuan; Hu, Bo; Sun, Jicheng; Yang, Zun; Yu, Wenliang; He, Zangmin; Gao, Xiang; Song, Jinlin] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China; [Pan, Shengyuan; Hu, Bo; Sun, Jicheng; Yang, Zun; Yu, Wenliang; He, Zangmin; Gao, Xiang; Song, Jinlin] Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China"

通信作者："Gao, X; Song, JL (通讯作者)，Chongqing Med Univ, Coll Stomatol, Chongqing, Peoples R China.; Gao, X; Song, JL (通讯作者)，Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China.; Gao, X; Song, JL (通讯作者)，Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000867951600001

JCR分区：Q1

影响因子：7.3

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：ferroptosis; drug prediction; periodontitis; type 2 diabetes mellitus; pathway

摘要："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-1 beta, 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."

基金机构：National Natural Science Foundation of China; Chongqing Research Program of Basic Research and Frontier Technology; Postgraduate Students' Innovative Research and Development Projects of Chongqing; [31600788]; [cstc2015jcyjA10035]; [CYB19158]; [dstd201903]

基金资助正文："Funding This study was supported by the National Natural Science Foundation of China (31600788), the Chongqing Research Program of Basic Research and Frontier Technology (cstc2015jcyjA10035), the Postgraduate Students' Innovative Research and Development Projects of Chongqing (CYB19158), 2019 Chongqing Graduate Tutor Team Construction Project (dstd201903)."