Abstract 102: Keap1/Nrf2 Dysfunction Impairs Wound Healing in Diabetes

RESULTS: In the wound bed, Keap1 siRNA treated mice decreased Keap1 gene expression (55.4 ± 22.9%; p=0.004) and protein expression (94 ± 0.42%; p=0.038) compared to controls. Downstream protein expression of Nrf2 increased (3.27 ± 1.63 fold; p=0.039). The expression of antioxidant genes, NQO-1 and MnSOD-1 increased (4.99 ± 0.1 fold; p=0.04 and 3.66 ± 0.2 fold; p=0.01, respectively). The expression of the chemokine, SDF-1 increased (7.51 ± 0.12 fold; p=0.01). Additionally, the expression of EGF increased (6.48 ± 0.15 fold; p=0.005). At day 10, the epithelial gap of Keap1 treated mice decreased compared to control mice (3.95 ± 0.21 mm vs 8.07 ± 1.37mm; p=0.004), granulation tissue increased (2.15 ± 0.65 mm vs 1.15 ± 0.44 mm; p= 0.049), and CD31+ cells/hpf increased (109.8 ± 17.96 vs 71.2 ± 27.32; p=0.02). Keap1 siRNA treated mice resulted in accelerated time to wound closure (22.3 ± 1.974 days vs 31 days; p=0.0213). Wound burden was decreased markedly by 57% compared to controls.