Regulation of connexin 43 expression in human gingival fibroblasts
Highlights: ●Wound healing-associated cytokines modulate connexin 43 abundance in human gingival fibroblasts. ●Interplay between these cytokines distinctly determines connexin 43 abundance via transcriptional/post-transcriptional and translational/post-translational mechanisms. ●TGF-β-induced upregulation of connexin 43 is mediated by SMAD2/3 pathway. ●TNF-α, IL-1β, IFN-γ and PGE2 inhibit TGF-β-induced connexin 43 upregulation by suppressing SMAD2/3 phosphorylation. Abundance of connexin 43 (Cx43), a transmembrane protein that forms hemichannels (HCs) and gap junctions (GJs), is dynamically regulated in human gingival fibroblasts (GFBLs) during wound healing. This may be important for fast and scarless gingival wound healing as Cx43 is involved in key cell functions important during this process. Our aim was to uncover the factors that regulate Cx43 expression and abundance in GFBLs. We hypothesized that cytokines and growth factors released during wound healing coordinately regulate Cx43 abundance in GFBLs.