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. 2024 Jan 19;19(1):e0296925.
doi: 10.1371/journal.pone.0296925. eCollection 2024.

Distinctive genes and signaling pathways associated with type 2 diabetes-related periodontitis: Preliminary study

Poliana Mendes Duarte  1 , Bruno César de Vasconcelos Gurgel  2 , Tamires Szeremeske Miranda  3 , Juliana Sardenberg  1 , Tongjun Gu  4 , Ikramuddin Aukhil  5
Affiliations

Distinctive genes and signaling pathways associated with type 2 diabetes-related periodontitis: Preliminary study

Poliana Mendes Duarte et al. PLoS One. .

Abstract

The biological mechanisms underlying the pathogenesis of type 2 diabetes (T2DM)-related periodontitis remain unclear. This cross-sectional study evaluated the distinctive transcriptomic changes between tissues with periodontal health and with periodontitis in patients with T2DM. In this cross-sectional study, whole transcriptome sequencing was performed on gingival biopsies from non-periodontitis and periodontitis tissues from non-diabetic and diabetic patients. A differentially expressed gene (DEG) analysis and Ingenuity Pathway Analysis (IPA) assessed the genes and signaling pathways associated with T2DM-related periodontitis. Immunohistochemistry was performed to validate selected DEGs possibly involved in T2DM-related periodontitis. Four hundred and twenty and one thousand five hundred and sixty-three DEGs (fold change ≥ 2) were uniquely identified in the diseased tissues of non-diabetic and diabetic patients, respectively. The IPA predicted the activation of Phagosome Formation, Cardiac β-adrenergic, tRNA Splicing, and PI3K/AKT pathways. The IPA also predicted the inhibition of Cholesterol Biosynthesis, Adrenomedullin, and Inositol Phosphate Compounds pathways in T2DM-related periodontitis. Validation of DEGs confirmed changes in protein expression of PTPN2, PTPN13, DHCR24, PIK3R2, CALCRL, IL1RN, IL-6R and ITGA4 in diseased tissues in diabetic subjects. Thus, these preliminary findings indicate that there are specific genes and functional pathways that may be involved in the pathogenesis of T2DM-related periodontitis.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1
IPA analysis of the canonical pathways related to the DEGs altered in tissues with periodontitis compared with tissues with periodontal health in non-diabetic patients. (A) The top ten dysregulated canonical signaling pathways are presented in descending order of statistical significance of −log(P-values). (B) The canonical pathways that were predicted to be modulated in the non-diabetic patients, as defined by a −log(P-value) >2 and Z-score <−1.3 (inhibited). (C) The number of upregulated and downregulated DEGs involved in each of the representative canonical pathways.
Fig 2
Fig 2. IPA analysis of the canonical pathways related to the DEGs altered in tissues with periodontitis compared with tissues with periodontal health in patients with T2DM.
(A) The top ten dysregulated canonical signaling pathways are presented in descending order of statistical significance of −log(P-values). (B) The canonical pathways that were predicted to be modulated in the non-diabetic patients, as defined by a −log(P-value) >2 and Z-score >2 (activated) or <−2 (inhibited). (C) The number of upregulated and downregulated DEGs involved in each of the representative canonical pathways.
Fig 3
Fig 3. The immunohistochemical staining using antibodies against PTPN2, PTPN13, DHCR24 (Seladin), and PIK3R2 in representative gingival biopsies from the HH, HP, DH, and DP groups.
Bar length = 50 μm, original magnification × 20. HH: non-diabetic patients without periodontitis; HP: non-diabetic patients with periodontitis; DH: T2DM patients without periodontitis; DP: T2DM patients with periodontitis.
Fig 4
Fig 4. The immunohistochemical staining using antibodies against CALCRL, IL1RN, IL6R, and ITGA4 in representative gingival biopsies from the HH, HP, DH, and DP groups.
Bar length = 50 μm, original magnification × 20. HH: non-diabetic patients without periodontitis; HP: non-diabetic patients with periodontitis; DH: T2DM patients without periodontitis; DP: T2DM patients with periodontitis.
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Grants and funding

PMD received a University of Florida College of Dentistry Faculty grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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