Downregulation of miRNA‐26 in chronic periodontitis interferes with innate immune responses and cell migration by targeting phospholipase C beta 1

• Published in: Journal of clinical periodontology Vol. 50; no. 1; pp. 102 - 113
• Main Authors: Uttamani, Juhi R., Naqvi, Afsar R., Estepa, Araceli Maria Valverde, Kulkarni, Varun, Brambila, Maria F., Martínez, Gloria, Chapa, Gabriela, Wu, Christine D., Li, Wei, Rivas‐Tumanyan, Sona, Nares, Salvador
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.01.2023
• Subjects: Actin; Biopsy; Cell adhesion & migration; Cell migration; Cell Movement; Chemokines; Chronic Periodontitis - genetics; Chronic Periodontitis - therapy; Cytokines; Cytokines - metabolism; Cytoskeleton; Down-Regulation; Gum disease; Humans; Immune response; Immunity, Innate; Innate immunity; Keratinocytes; Lipopolysaccharides; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Original; Pathogenesis; Periodontitis; Phospholipase C; Phospholipase C beta - metabolism; Wound healing; phospholipase C; cell migration; microRNA; cytoskeleton; periodontitis
• ISSN: 0303-6979; 1600-051X; 1600-051X
• DOI: 10.1111/jcpe.13715

Aim To evaluate the potential role of miR‐26 family members in periodontal pathogenesis by assessing innate immune responses to periopathic bacteria and regulation of cytoskeletal organization. Materials and Methods Expression of miR‐26a‐5p and miR‐26b‐5p was quantified in gingival biopsies derived from healthy and periodontally diseased subjects before and after non‐surgical (scaling and root planing) therapy by RT‐qPCR. Global pathway analysis and luciferase assays were performed for target identification and validation. Cytokine expression was assessed in miR‐26a‐5p transfected human oral keratinocytes upon stimulation with either live Porphyromonas gingivalis (Pg), Aggregatibacter actinomycetemcomitans or Pg lipopolysaccharide (LPS). Wound closure assays were performed in cells transfected with miR‐26a‐5p, while the impact on cytoskeletal organization was assessed by F‐actin staining. Results miR‐26a‐5p and miR‐26b‐5p were downregulated in diseased gingiva and restored 4–6 weeks post‐therapy to levels comparable with healthy subjects. Target validation assays identified phospholipase C beta 1 as a bona fide novel target exhibiting antagonistic expression pattern in disease and post‐therapy cohorts. miR‐26a‐5p transfected cells secreted higher levels of cytokine/chemokines upon stimulation with periopathogens and demonstrated impaired cell migration and cytoskeletal rearrangement. Conclusions Downregulated miR‐26a‐5p levels in periodontal inflammation may interfere with key cellular functions that may have significant implications for host defence and wound healing.