Comprehensive analysis of transcriptome and pathway interactions in periodontitis

Bruno César de Vasconcelos Gurgel; Nathalia Vilela; Kaio Henrique Soares; Ikramuddin Aukhil; Poliana Mendes Duarte; Luiz Eduardo Rodrigues Juliasse

doi:10.1590/

Authors

Bruno César de Vasconcelos Gurgel Universidade Federal do Rio Grande do Norte. Departamento de Odontologia https://orcid.org/0000-0001-5971-134X
Nathalia Vilela Universidade de São Paulo. Faculdade de Odontologia. Departamento de Estomatologia. Divisão de Periodontia https://orcid.org/0000-0002-0111-2309
Kaio Henrique Soares Universidade Federal do Rio Grande do Norte. Departamento de Odontologia https://orcid.org/0000-0002-1239-9296
Ikramuddin Aukhil East Carolina University. ECU School of Dental Medicine https://orcid.org/0000-0002-7127-3693
Poliana Mendes Duarte University of Florida College of Dentistry, Department of Periodontology, Gainesville, F https://orcid.org/0000-0001-8872-5943
Luiz Eduardo Rodrigues Juliasse Universidade Federal do Rio Grande do Norte. Departamento de Odontologia https://orcid.org/0009-0009-9697-4777

DOI:

https://doi.org/10.1590/

Keywords:

Periodontitis, Transcriptome, Gene expression and regulatory networks, Bioinformatics, RNA sequencing

Abstract

Periodontitis involves complex immune, epithelial, and metabolic disruptions. High-throughput transcriptomic approaches can reveal key regulatory networks underpinning disease progression. Objective To investigate the transcriptomic profile and dysregulated molecular pathways associated with severe periodontitis. Methodology Gingival tissues from patients with severe periodontitis (n=11) and periodontally healthy controls (n=11) were compared using RNA sequencing in this cross-sectional study. Differentially expressed genes (DEGs) were identified and analyzed using Ingenuity Pathway Analysis (IPA). Selected DEGs were validated at the protein level via immunohistochemistry (IHC). Results A total of 909 DEGs were upregulated and 742 were downregulated in periodontitis versus healthy tissues. Highly upregulated genes included MT-RNR1, MTRNR2L12, pseudogenes, long non-coding RNAs, and immunoglobulins. Downregulated genes included ADGRG7, C6orf15, members of enzyme families, keratin family members, loricrin (LOR), and immune modulators, such as CD207 (Langerin) and DEFB4A. IPA predicted the Wnt/β-catenin pathway as the most upregulated and the IL-17 signaling pathway as the most suppressed canonical pathway in periodontitis. The expression of the level of protein of LOR, Wnt10b, JUN, and FOS was confirmed by IHC. Conclusion Dysregulation in key canonical signaling pathways and the altered expression of genes critical to cell chemotaxis, innate immunity, and epithelial barrier integrity seem to play a pivotal role in the pathogenesis of periodontitis.

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Comprehensive analysis of transcriptome and pathway interactions in periodontitis

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