Inhibition of TGFβ1/Smad pathway by NF-κB induces inflammation leading to poor wound healing in high glucose

This study mainly analyzed the relationship between nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor-β (TGFβ1)/Smad under high glucose environment and its influence on wound healing. Fibroblast NIH-3T3 was used to analyze the effect of high concentration glucose (20 nmol/mL) on cell viability, migration ability, inflammation level and NF-κB pathway. Pyrrolidinedithiocarbamate (PDTC) was used to inhibit NF-κB for rescue experiments. Diabetic mice were used to construct wound healing models. Recombinant TGF-β1 was used to promote wound healing in diabetic mice. FSL-1 was applied to activate NF-κB to verify the mechanism. High glucose inhibited cell viability and migration ability, promoted the expression of TNF-α, IL-6 and IL-1β, induced the activation of NF-κB pathway in fibroblasts. Inhibition of NF-κB not only blocked the decrease in cell viability and migration ability induced by high glucose, but also relieved the release of inflammatory factors. TGF-β1 activated the TGF-β1/Smad pathway and promoted wound healing in diabetic mice. Activating the NF-κB pathway not only inhibited the activation of the TGF-β1/Smad pathway, but also alleviated the promoting effect of TGF-β1 on wound healing. In a high glucose environment, the activation of NF-κB may inhibit the function of fibroblasts by inhibiting the TGF-β1/Smad pathway, resulting in poor wound healing.