Chronic wounds are a serious and debilitating complication of diabetes. A better understanding of the
dysregulated healing responses following injury will provide insight into the optimal time frame for
therapeutic intervention. In this study a direct comparison was done between the healing dynamics and
the proteome of acute and obese diabetic wounds on day 2 and day 7 following injury. Full thickness
excisional wounds were induced on obese diabetic (B6.Cg-lepob/J, ob/ob, n=14) (blood glucose
423,25±127,92 mg/dL) and wild-type control (C57BL/6J, n=14) (blood glucose 186,67±24,5 mg/dL)
mice. Histological analysis showed no signs of healing in obese DM wounds whereas complete wound
closure/ re-epithelization, the formation of granulation tissue and signs of re-vascularization was evident
in acute wounds on day 7. In obese DM wounds, substance P deficiency and increased MMP-9 activity
on day 2 coincided with increased cytokine/chemokine levels within wound fluid. LC-MS/MS identified
906 proteins, of which 23 (Actn3, Itga6, Epb41, Sncg, Nefm, Rsp18, Rsp19, Rpl22, Macroh2a1, Rpn1,
Ppib, Snrnp70, Ddx5, Eif3g, Tpt1, FABP5, Cavin1, Stfa1, Stfa3, Cycs, Tkt, Mb, Chmp2a) were
differentially expressed in wounded tissue on day 2 (p<0.05; >2 fold) and 6 (Cfd, Ptms, Hp, Hmga1,
Cbx3, Syap1) (p<0.05; >2 fold) on day 7. A large number of dysregulated proteins on day 2 was
associated with an inability to progress into the proliferative stage of healing and suggest that early
intervention might be pivotal for effective healing outcomes. The proteomic approach highlighted the
complexity of obese DM wounds in which the dysregulation involves multiple regulatory pathways and
biological processes.
