Whole mount sections through the area of wounded skin and examined under light microscopy (a) or, of the same section with DAPI staining of nuclei (b) include a central disorganized zone, the wound margin and nearby adjacent normal epidermis (white arrows) [Bar=500 microns].

<p>The schematic shows the variation of epidermal thickness from normal skin [left arrows; left and right sides of the Figure] to the new tissue ingrowth zone [right arrow; center of the Figure] (c) is matched to tissue zones with normal appearing epidermis and dermis (d), epidermis and dermis directly adjacent to the wound site (e) and new tissue growing by secondary intent into the previously biopsied zone (f). There were no differences in thickness of these zones at 7d following injury between nondiabetics and diabetics (solid bar=nondiabetics, hatched=diabetics; n=5 diabetic, 5 nondiabetic). Note C=control nondiabetic; D=diabetic.</p

Rac1 (a) was elevated in day 7 wounds (N - nondiabetic,D-diabetic; NI,DI-injury wound zone; NA,DA- adjacent to wound) [ANOVA p=0.0004; post hoc *p<0.05 for N vs. NI and D vs. DI; n=3/group].

<p>RHOA (b) increased in diabetics following injury [ANOVA p<0.0001; post hoc *p<0.05 for NI vs. DI, D vs. DI; n=3/group]. PTEN (c) was elevated after injury [ANOVA p=0.0006; post hoc *p<0.05 for N <a href="http://vs.ni" target="_blank">vs.NI</a> and D vs. DI; n=3/group]. PTEN was localized in subepidermal axons (arrows) and diffusely in keratinocytes and dermal connective tissue (nondiabetic intact skin (d) or adjacent to wound (e) and diabetic adjacent to wound (f)) [Bar=33 microns]. There was widespread PTEN rise in the central wound zone and adjacent skin [nondiabetic illustrated by wholemount (g) [Bar=200 microns].</p

GAP43 axon innervation of three zones associated with dorsal skin wounds (black arrows) shown by the schematic to be from nearby normal skin (a,d), adjacent wound margins (b,e) and the wound zone healing by secondary intention (c,f).

<p>Images (a-c) are nondiabetic littermate controls and (d-f) from diabetic mice. Data are matched to the wound zone in the micrographs above them (g,j nearby normal skin; h,k adjacent wound margin; i,l wound zone). Graphs show vertically directed GAP 43 axon density (g-i) and total GAP43 axon density (j-l) in diabetics (open bars) and nondiabetics (black bars). [g *p<0.05; h p=0.06 (NS) diabetic vs. nondiabertic; k *p<0.05 diabetic vs. nondiabetic, one tailed Student’s t-test; n=3 diabetic, 3 nondiabetic]. Bar=20 microns. </p