VPA treatment further accelerates cutaneous wound healing in CXXC5−/− mice. After generation of full-thickness wounds (diameter = 1.5 cm) on the backs of CXXC5+/+ and CXXC5−/− mice, 500 mM VPA was applied topically to the wounds daily (n = 10 mice/group). (A) Representative images of macroscopic wounds, H&E, and IHC staining showing expression of β-catenin, CXXC5, keratin 14, collagen I, and PCNA in the wounds of CXXC5+/+ and CXXC5−/− mice treated with or without VPA treatment 12 d after wounding (n = 4 mice/group) are shown (n = 3 independent experiments). Dashed lines indicate the epidermal–dermal boundary. F, fibroblasts; K, keratinocytes. (B) Relative wound closure rates describe the effects of VPA on wound healing in CXXC5+/+ and CXXC5−/− mice. Wound sizes were measured at 1, 3, 5, 7, 9, and 12 d after wounding (**, P < 0.005; ***, P < 0.0005; n = 10 mice/group). (C) Western blot analyses of β-catenin, CXXC5, keratin 14, α-SMA, collagen I, PCNA, endothelin-1, c-Myc, cyclin D1, and Erk were performed in wounds of CXXC5+/+ and CXXC5−/− mice treated with or without VPA (n = 2 mice/group) 12 d after wounding (n = 2 independent experiments). Relative densitometry values are shown below blots. (D) Representative images of Masson’s trichrome, picrosirius red, or van Gieson staining of wounds of CXXC5+/+ and CXXC5−/− mice treated with or without VPA 12 d after wounding (n = 4 mice/group) are shown (n = 3 independent experiments). (A and D) Bars, 100 µm. (E) Hydroxyproline levels in wounds of CXXC5+/+ and CXXC5−/− mice treated with or without VPA 12 d after wounding are shown (*, P < 0.05; **, P < 0.005; ***, P < 0.0005; n = 4 mice/group). (F) Quantitative TissueFAXS analyses of IHC staining shown in A were performed in keratinocytes (left) and fibroblasts (right; *, P < 0.05; **, P < 0.005; ***, P < 0.0005; n = 3 independent experiments). Means ± SD.