rhaFGF promotes acute diabetic wound healing by suppressing chronicity of inflammation

To investigate the effect of recombinant human aFGF (rhaFGF) on acute wounds in a diabetic mouse model focusing on the transition from acute inflammation to chronic inflammation. Diabetes mellitus (DM) mouse models were induced through intraperitoneal injection of streptozotocin and acute diabetic wounds were created on their hind paws. The mice were divided into four groups: Con, Con + rhaFGF, DM, and DM + rhaFGF. rhaFGF (0.08 mu g/cm(2)) or PBS was daily administered on wound surface for 14 days. The levels of IL-6 and TNF-alpha in serum and tissues were measured using ELISA, and NLRP3 inflammasome components (NLRP3, ASC and caspase-1) and pro-inflammatory cytokines (IL-1 beta, IL-18) in tissue were detected by Western blot analysis. CCK8 assay and cell migration were used to assess the proliferation and migration ability of HUVEC, HFF, and HaCaT cells, respectively. Wound healing rates in the DM group decreased significantly, which was effectively alleviated by rhaFGF treatment for 7 days and longer durations. Notably, at day 7 after wound creation, the levels of IL-6 and TNF-alpha as well as the expressions of NLRP3, ASC, caspase-1, IL-1 beta, and IL-18 in the DM group were significantly increased, and rhaFGF treatment substantially suppressed these changes. Moreover, when HUVEC, HFF, and HaCaT cells were exposed to high glucose and LPS condition, the proliferation and migration of these cells were significantly inhibited, and rhaFGF treatment effectively reversed this inhibition. rhaFGF could promote the healing of acute DM wounds by preventing chronicity transition of acute inflammation via reducing the release of pro-inflammatory cytokines and inhibiting the activation of NLRP3 in DM wounds.