Akt1 and Akt2 are essential for both normal wound healing and efficacy of eHsp90α in mice. (A) Full-thickness excision wounds (1.0 cm by 1.0 cm) were created on the backs of Akt2 knockout mice. The wounds were treated with placebo (5% CMC, carboxymethycellulose gel) or CMC containing recombinant Hsp90α (30 μg/ml). The images of one representative experiment are shown between day 0 and the day 5. (B) Mean error of percentage of wound closure on day 5 ± SD, in reference to day 0 wounds. (C and D) Similar analyses were carried out using Akt1 knockout mice, except that 0.7-cm by 0.7-cm wounds (due to the smaller sizes of Akt1 knockout mice) were created. (E and F) H&E staining of day 14 full-thickness wound sections from either placebo (CMC)- or recombinant Hsp90α-treated wounds. A total of nine randomly selected images per condition from three independent experiments were analyzed. Representative images are shown. The unhealed wound gaps are indicated by red and yellow lines. Magnification bars, 7.5 μm. ReT, reepithelialization tongue (green lines), indicating the newly migrated keratinocytes at the wound edges.