Gingival tissue autophagy pathway gene expression profiles in periodontitis and aging

Jeffrey L. Ebersole, Sreenatha Kirakodu, Michael J. Novak, Dolph Dawson, Arnold J. Stromberg, Luis Orraca, Janis Gonzalez-Martinez, Armando Burgos, Octavio A. Gonzalez

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Objective: We hypothesized that autophagy-related genes will be differentially expressed in periodontitis, suggesting an impaired gingival autophagic response associated with disease. Background: Autophagy is a cellular physiologic mechanism to maintain tissue homeostasis, while deficient autophagic responses increase inflammation and susceptibility to infection. Methods: Rhesus monkeys [<3 years to 23 years of age (n = 34)] were examined for periodontal health and naturally occurring periodontitis. Gingival tissues samples were obtained from healthy or diseased sites, total RNA was isolated, and the Rhesus Gene Chip 1.0 ST (Affymetrix) was used for gene expression analysis of 150 autophagy-related genes. Results: Comparison of expression levels with adult healthy tissues demonstrated a rather limited number of individual genes that were significantly different across the age-groups. In contrast, with periodontitis in the adults and aged animals, about 15% of the genes were significantly increased or decreased. The differences were reflected in the mTOR complex (5/12), ULK1/ATG1 complex (5/9), PI3K complex (5/21), ATG9 complex (2/7), ATG12 conjugation/LC3 lipidation (7/22), and lysosome fusion/vesicle degradation [LF/VD (5/10)] activities within the broader autophagic pathway. The genes most greatly altered in gingival tissues of naturally occurring periodontitis were identified in the ATG12 and LF/VD pathways that approximated 50% of the genes in each of those categories. While healthy gingival aging did not appear to reflect altered autophagy gene expression, substantial differences were noted with periodontitis irrespective of the age of the animals. Future studies into the role of autophagy in periodontitis and could offer potential new therapeutic strategies to prevent and/or treat periodontal disease.

Original languageEnglish
Pages (from-to)34-45
Number of pages12
JournalJournal of Periodontal Research
Volume56
Issue number1
DOIs
StatePublished - Jan 2021

Bibliographical note

Publisher Copyright:
© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Keywords

  • autophagy
  • gene expression
  • nonhuman primates
  • periodontitis

ASJC Scopus subject areas

  • Periodontics

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