Inhibition of the receptor for advanced glycation promotes proliferation and repair of human periodontal ligament fibroblasts in response to high glucose via the NF-κB signaling pathway

•The high RAGE expression in high glucose might cause damage of periodontal tissue.•A new drug target promote the repair the damage caused by high glucose in hPDLFs.•A new micromolecular drug might be feasible to cure oral diabetic complication. To observe if inhibition of the receptor for advanced glycation endproducts (RAGE) promotes proliferation and repair of human periodontal ligament fibroblasts (hPDLFs) stimulated by high glucose. In addition, we also discuss the effects of the NF-κB signaling pathway in relation to this process. Primary cultured hPDLFs were exposed to either low glucose (5.5 mmol/L) or high glucose (25 mmol/L), and RAGE expression was measured by Western blot analysis. Cells were cultured in high glucose with different concentrations of the RAGE inhibitor, FPS-ZM1. We measured cell proliferation using the Cell Counting Kit-8 and expression of collagen type 1 and fibronectin by real-time PCR and ELISA, respectively. The relative protein expression levels of NF-κB p65 and phosphorylated p65 were measured by Western blot analysis. High glucose enhanced RAGE expression and suppressed cell growth. While FPS-ZM1 increased proliferation and expression of repair-related factors in high glucose, there was a concurrent decline in the phosphorylation level of NF-κB p65. FPS-ZM1 rescued the proliferative capacity and repair capability of hPDLFs via the RAGE-NF-κB signaling pathway in response to high glucose.