In diabetes mellitus, dysfunctional endothelial cells (EC) and low numbers of endothelial progenitor cells (EPC) in the peripheral circulation lead to several vascular disorders like impaired wound healing. Recent reports indicate reactive oxygen species (ROS) and low expression of the cytokine, stromal cell-derived factor-1? (SDF-1?) to be important causes of these pathological conditions. As neurotransmitter dopamine (DA) is reported to regulate ROS production and because DA may also control SDF-1? synthesis, we therefore hypothesized that DA could normalize EC functions and SDF-1? expression in diabetic wound tissues.
Aim 1 will investigate the effect of DA D1 receptors on ROS induced EC functions.
In Aim 2, the role of DA D1 receptors on SDF-1? production by macrophages will be determined and finally Aim 3 will examine the effects of DA D1 receptors on ROS production and neovascularization in diabetic wound tissues.
Endothelial cell dysfunctions and significantly decreased production of growth factors and cytokines in diabetes mellitus lead to several vascular disorders like impaired wound repair and healing. According to the Center for Disease Control and Prevention, refractory diabetic wounds lead to over 72,000 amputations each year despite of advances in wound care, therefore the goal of this application is to develop dopamine mediated newer and an effective therapy for this pathological condition.
|Roy, Soumyabrata; Lu, Kai; Nayak, Mukti Kant et al. (2017) Activation of D2 Dopamine Receptors in CD133+ve Cancer Stem Cells in Non-small Cell Lung Carcinoma Inhibits Proliferation, Clonogenic Ability, and Invasiveness of These Cells. J Biol Chem 292:435-445|
|Chakroborty, Debanjan; Sarkar, Chandrani; Lu, Kai et al. (2016) Activation of Dopamine D1 Receptors in Dermal Fibroblasts Restores Vascular Endothelial Growth Factor-A Production by These Cells and Subsequent Angiogenesis in Diabetic Cutaneous Wound Tissues. Am J Pathol 186:2262-70|
|Lu, Kai; Bhat, Madhavi; Basu, Sujit (2016) Plants and their active compounds: natural molecules to target angiogenesis. Angiogenesis 19:287-95|
|Kanji, Suman; Das, Manjusri; Aggarwal, Reeva et al. (2014) Nanofiber-expanded human umbilical cord blood-derived CD34+ cell therapy accelerates murine cutaneous wound closure by attenuating pro-inflammatory factors and secreting IL-10. Stem Cell Res 12:275-88|