Gene expression profiles of mitochondria-endoplasmic reticulum tethering

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 glucoseregulated 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 mu g/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-alpha (TNF-alpha), 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-alpha 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.

C1 [Aral, Kubra; Milward, Michael R.; Cooper, Paul R.] Univ Birmingham, Sch Dent, Birmingham, W Midlands, England.

[Cooper, Paul R.] Univ Otago, Fac Dent, Sir John Walsh Res Inst, Dunedin, New Zealand.

[Aral, Kubra] Inonu Univ, Fac Dent, Dept Periodontol, Malatya, Turkey.