Diabetes Mellitus (DM) affects about 425 million people worldwide. These patients are often afflicted with lower extremity ulcers which account for about 60% of non-traumatic lower limb amputations. This results in high morbidity and mortality, with a significant loss in quality of life and socioeconomic impact. Conventional treatment for diabetic wounds is restricted to bandages and debridement. Besides being painful, these procedures are generally time-consuming and require patient cooperation. Newer approaches that can assist these patients that are rime and cost effective are necessary. The therapeutic use of low dose light treatments is termed Photobiomodulation (PBM) therapy. PBM treatments have demonstrated reduced pain improved cell proliferation supporting tissue repair and wound healing in diabetic patients. There are three well described mechanisms involving cytochrome c oxidase, cell membrane receptors or transporters and extracellular latent TGF-B1 activation. However, their roles in diabetes remain to be fully investigated. Herein we aim to evaluate the roles of PBM-activated TGF-B1 on MMP-9 in modulating tissue remodeling by endothelial cells under hyperglycemic conditions in vitro. To develop a sound mechanistic rationale for the use PBM treatments in diabetic wound healing, we propose examining a) the effect of PBM treatments on endothelial cell proliferation, migration and budding; b) Effects of PBM treatment on angiogenesis mediated by VEGF and TGF-B1; c) Effects of PBM treatments on tissue remodeling mediated via TGF-B1/ MMP-9 signaling and d) validate the role of these signaling pathways using specifics inhibitors and siRNA. These results will help in consolidating the role of PBM therapy for the treatment of diabetic wounds.
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