132 Differential Regulation of Osteopontin and Matrix Metalloproteinases During Diabetic Wound Healing

Abstract

Delayed wound healing is a common complication of diabetes resulting in significant clinical morbidity. The diabetic wound exhibits impaired cellular infiltration and consequently inadequate granulation tissue formation. Additionally, altered patterns of apoptosis. In this study, we have evaluated the differential gene expression pattern in transgenic diabetic female mice, 5–6 weeks old, in a full thickness cutaneous punch wound model. We assessed the role of matrix metalloproteinases (MMPs) and differential gene expression pattern at 4th, 7th and 11th day post wounding. Supernatants obtained from diabetic wound tissue homogenates were subjected to zymogram analysis. The data showed that MMPs were expressed at higher level by 4th day post wounding, whereas expression of MMPs were down regulated towards the 11th day post wounding suggesting their role during early phase of wound healing.The pathway specific gene array data demonstrated differential regulation of several growth factors, transcription factors and other related genes such as fibroblast growth factors and their receptors, ID3 and restin respectively. The cytokine/extracellular matrix protein osteopontin (OPN), an important component of cellular immunity and inflammation also showed higher expression after 4 days post wounding. The expression of OPN remained at higher level after 11 days post wounding in diabetic mice, whereas the expression were down regulated to basal level in normal wounded animal suggesting that the expression of OPN was concomitant with the extent of healing. Other adhesion molecules such as integrin αV and PECAM‐1 were also differentially regulated. Though a single gene may not be solely responsible for any defect or impairment in healing as it is a very tightly controlled and regulated process, however, a detailed study of these gene(s) may shed some light to the delayed healing in diabetic mice. Acknowledgements: (These studies are supported by NIH Grant G174KT.)