Akt/hypoxia-inducible factor-1α signaling deficiency compromises skin wound healing in a type 1 diabetes mouse model.

The aim of the present study was to investigate the mechanisms for impaired skin wound healing in subjects with diabetes. Type 1 diabetes (T1DM) was induced in BALB/c mice using streptozotocin. One month after the establishment of the T1DM mouse model, a wound was formed on the back of the mice, and tissues from the wounds and the margins were collected on days 0, 3, 7 and 10. Protein levels of cluster of differentiation 31 (CD31) were detected using immunohistochemistry, and the mRNA levels of Akt, hypoxia-inducible factor-1α (Hif-1α), vascular endothelial growth factor (Vegf), VEGF receptor 2 (Vegfr2), stromal cell-derived growth factor-1α (Sdf-1α) and CXC chemokine receptor 4 (Cxcr4) were determined using reverse transcription-quantitative polymerase chain reaction analysis. The corresponding protein levels were determined using western blotting. The skin wound healing rate in the T1DM mice was significantly lower than that in the control mice, and the protein level of CD31 in the wounded skin of the T1DM mice was significantly decreased. Furthermore, the overall mRNA levels of Akt, Hif-1α, Vegf, Vegfr2, Sdf-1α and Cxcr4 in the T1DM mice were significantly lower than those in the control mice, and similar trends were observed in the protein levels. In conclusion, skin wound healing was impaired in the T1DM mice, and this may have been caused by a deficiency of Akt/HIF-1α and downstream signaling, as well as delayed angiogenesis.