Directed expression of Hox A3 upregulates target genes associated with wound healing in diabetic mice

Abstract

Abstract Introduction: Poor wound healing in diabetic patients is associated with deficiencies in the production of growth factors, collagen, and other proteins involved in cell proliferation and migration. However, it remains unclear how the diabetic environment affects regulation of these molecules in response to wounding at the level of gene transcription. We hypothesized that Hox A3 could accelerates diabetic wound healing through activation of target genes that promote angiogenesis and cell migration. Methods: Hox A3 and control plasmids were transfected into cells and wounds from wild type and leptin receptor deficient diabetic mice. Wounds were analyzed for up to 40 days, depending on initial size. Protein levels were measured by Western blot analysis. Hox A3 target gene activation was assayed by semi-quantitative PCR and quantitative real time PCR. Results: Directed Hox A3 expression in diabetic wounds dramatically accelerated wound healing as wounds closed at day 42 compared to the control, day 77 (p Conclusions: Hox A3 function is dramatically reduced in diabetic wounds and is associated with poor wound healing. Restoring Hox A3 expression significantly accelerates wound healing and is therefore a potential therapeutic target in diabetic patients. Further studies are underway to determine why diabetic cells fail to activate Hox A3.