Differential regulation of angiogenic genes in diabetic wound healing.

Wound healing is a complicated biological process that involves interactions of multiple cell types, various growth factors, their mediators, and the extracellular matrix proteins. In this study, we have studied the differential regulation of angiogenic genes during wound healing in transgenic (Lepr -/-) diabetic mice and non-diabetic mice. Under aseptic conditions, 8 mm full thickness cutaneous wounds were created on either side of the mid-dorsal. Wound tissues were studied at 4, 7, and 11 days post-wounding and healing was assessed by histology. The pathway-specific gene array data demonstrated differential regulation of growth factors, transcription factors, and other related genes, such as fibroblast growth factors and their receptors. The extracellular matrix protein osteopontin (OPN), an important component of cellular immunity and inflammation, showed higher expression in non-diabetic wounds after 4 days post-wounding, whereas its expression was at basal level in diabetic wounds. OPN expression remained upregulated in non-diabetic wounds at day 7 post-wounding and was downregulated to basal level at day 11 post-wounding. However, expression of OPN was upregulated in diabetic wounds at day 7 post-wounding and remained constitutively higher at day 11 post-wounding. OPN expression was concomitant with the extent of healing as assessed by histology at the corresponding sampling point. This finding suggests that OPN might be playing a crucial role in the early events of the wound healing and its delayed expression may be in part responsible for the delayed healing of wounds in diabetic mice.