Gene expression profiles of mitochondria-endoplasmic reticulum tethering in human gingival fibroblasts in response to periodontal pathogens

Kübra Aral; Michael R Milward; Paul R Cooper

doi:10.1016/j.archoralbio.2021.105173

Gene expression profiles of mitochondria-endoplasmic reticulum tethering in human gingival fibroblasts in response to periodontal pathogens

Arch Oral Biol. 2021 Aug:128:105173. doi: 10.1016/j.archoralbio.2021.105173. Epub 2021 May 27.

Authors

Kübra Aral¹, Michael R Milward², Paul R Cooper³

Affiliations

¹ School of Dentistry, University of Birmingham, Birmingham, UK; Department of Periodontology, Faculty of Dentistry, Inonu University, Malatya, Turkey. Electronic address: drkubraaral@gmail.com.
² School of Dentistry, University of Birmingham, Birmingham, UK.
³ School of Dentistry, University of Birmingham, Birmingham, UK; Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, Dunedin, New Zealand.

PMID: 34058723
DOI: 10.1016/j.archoralbio.2021.105173

Abstract

Objective: The current study aimed to elucidate the potential involvement of mitochondria-endoplasmic reticulum contact genes in the pathogenesis of periodontal disease by monitoring levels of contact associated genes including Mitofusion 1 (MFN1) and MFN2, inositol 1,4,5-trisphosphate receptor (IP3R), chaperone glucose-regulated protein 75 (GRP75), sigma non-opioid intracellular receptor 1 (SIGMAR1) and phosphate and tensin homolog induced putative kinase 1 (PINK1) in human gingival fibroblasts in response to periodontal pathogens Fusobacterium nucleatum (F. nucleatum) and Porphyromonas gingivalis (P. gingivalis) in vitro.

Design: Primary human gingival fibroblasts were exposed to live cultures of P. gingivalis (W83; ATCC BAA-308) and F. nucleatum (subsp. Polymorphum; ATCC 10953) alone or in combination for 4 h at a 50 or 200 multiplicity of infection. Escherichia coli lipopolysaccharide (10 μg/mL) exposure was used as a positive control. Gene expression levels of contact genes (MFN1, MFN2, IP3R, GRP75, SIGMAR1 and PINK1) as well as a proinflammatory cytokine, Tumor necrosis factor-α (TNF-α), and the apoptosis associated gene, Immediate early response 3 (IER3), were evaluated by reverse transcription polymerase chain reaction analysis.

Results: MFN1, GRP75, IP3R and PINK1 were significantly upregulated by P. gingivalis with or without F. nucleatum. Only P. gingivalis with F. nucleatum caused a significant upregulation of SIGMAR1. TNF-α and IER3 gene expression positively correlated with the contact-associated gene expression changes.

Conclusion: F. nucleatum and P. gingivalis alone or in combination may differentially dysregulate the gene expression levels of contact-associated genes in human gingival fibroblasts. These host-microbiome interactions may mechanistically be important in the pathogenesis of periodontal disease.

Keywords: Endoplasmic reticulum; Fusobacterium nucleatum; Gingival fibroblasts; Mitochondria; Periodontal disease; Porphyromonas gingivalis.

MeSH terms

Endoplasmic Reticulum
Fibroblasts
Fusobacterium nucleatum
Gingiva*
Humans
Mitochondria
Porphyromonas gingivalis
Transcriptome*