Exploration of Shared Gene Signatures and Molecular Mechanisms Between Periodontitis and Nonalcoholic Fatty Liver Disease

Wanqiu Xu; Zhengwei Zhang; Lihong Yao; Bing Xue; Hualei Xi; Xiumei Wang; Shibo Sun

doi:10.3389/fgene.2022.939751

Exploration of Shared Gene Signatures and Molecular Mechanisms Between Periodontitis and Nonalcoholic Fatty Liver Disease

Front Genet. 2022 Jun 28:13:939751. doi: 10.3389/fgene.2022.939751. eCollection 2022.

Authors

Wanqiu Xu¹, Zhengwei Zhang², Lihong Yao¹, Bing Xue¹, Hualei Xi¹, Xiumei Wang¹, Shibo Sun²

Affiliations

¹ Department of Dentistry, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
² Ward 7, Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Abstract

Background: Periodontitis is associated with periodontal tissue damage and teeth loss. Nonalcoholic fatty liver disease (NAFLD) has an intimate relationship with periodontitis. Nevertheless, interacted mechanisms between them have not been clear. This study was intended for the exploration of shared gene signatures and latent therapeutic targets in periodontitis and NAFLD. Methods: Microarray datasets of periodontitis and NAFLD were obtained from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network analysis (WGCNA) was utilized for the acquisition of modules bound up with NAFLD and periodontitis. We used ClueGO to carry out biological analysis on shared genes to search their latent effects in NAFLD and periodontitis. Another cohort composed of differential gene analysis verified the results. The common microRNAs (miRNAs) in NAFLD and periodontitis were acquired in the light of the Human microRNA Disease Database (HMDD). According to miRTarbase, miRDB, and Targetscan databases, latent target genes of miRNAs were forecasted. Finally, the miRNAs-mRNAs network was designed. Results: Significant modules with periodontitis and NAFLD were obtained via WGCNA. GO enrichment analysis with GlueGo indicated that damaged migration of dendritic cells (DCs) might be a common pathophysiologic feature of NAFLD and periodontitis. In addition, we revealed common genes in NAFLD and periodontitis, including IGK, IGLJ3, IGHM, MME, SELL, ENPP2, VCAN, LCP1, IGHD, FCGR2C, ALOX5AP, IGJ, MMP9, FABP4, IL32, HBB, FMO1, ALPK2, PLA2G7, MNDA, HLA-DRA, and SLC16A7. The results of differential analysis in another cohort were highly accordant with the findings of WGCNA. We established a comorbidity model to explain the underlying mechanism of NAFLD secondary to periodontitis. Finally, the analysis of miRNA pointed out that hsa-mir-125b-5p, hsa-mir-17-5p, and hsa-mir-21-5p might provide potential therapeutic targets. Conclusion: Our study initially established a comorbidity model to explain the underlying mechanism of NAFLD secondary to periodontitis, found that damaged migration of DCs might be a common pathophysiological feature of NAFLD and periodontitis, and provided potential therapeutic targets.

Keywords: WGCNA; dendritic cell migration; miRNAs–mRNAs; nonalcoholic fatty liver disease; periodontitis.