title: 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.
abstract: In wound beds, fibroblasts are rich sources of vascular endothelial growth factor A, a cytokine necessary for promoting angiogenesis and thereby the healing of wound tissues. However, in diabetes mellitus, these cells are functionally impaired and produce reduced amounts of vascular endothelial growth factor A, resulting in deficient angiogenesis and delayed wound healing. We here for the first time demonstrate that stimulation of D1 dopamine receptors present in dermal fibroblasts restores vascular endothelial growth factor A production by these cells, resulting in adequate angiogenesis and subsequent healing of cutaneous wounds in both type 1 and type 2 diabetic mice. This action of D1 dopamine receptors was mediated through the protein kinase A pathway. As delayed wound healing or chronic wounds are one of the major health problems in diabetic patients, D1 dopamine receptor agonists, which are already in clinical use for the treatment of other disorders, may be of translational value in the treatment of chronic, nonhealing diabetic wounds.
authors.affiliation: Department of Pathology, Ohio State University, Columbus, Ohio.
authors.forename: Debanjan
authors.initials: D
authors.lastname: Chakroborty
authors.affiliation: Department of Pathology, Ohio State University, Columbus, Ohio.
authors.forename: Chandrani
authors.initials: C
authors.lastname: Sarkar
authors.affiliation: Department of Pathology, Ohio State University, Columbus, Ohio.
authors.forename: Kai
authors.initials: K
authors.lastname: Lu
authors.affiliation: Department of Pathology, Ohio State University, Columbus, Ohio.
authors.forename: Madhavi
authors.initials: M
authors.lastname: Bhat
authors.affiliation: Chittaranjan National Cancer Institute, Kolkata, India. Electronic address: partha42002@yahoo.com.
authors.forename: Partha Sarathi
authors.initials: PS
authors.lastname: Dasgupta
authors.affiliation: Department of Pathology, Ohio State University, Columbus, Ohio; Division of Medical Oncology, Department of Internal Medicine, Ohio State University, Columbus, Ohio. Electronic address: sujit.basu@osumc.edu.
authors.forename: Sujit
authors.initials: S
authors.lastname: Basu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D018919:Neovascularization, Physiologic / Q000502:physiology*; D016133:Polymerase Chain Reaction; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D017447:Receptors, Dopamine D1; D042461:Vascular Endothelial Growth Factor A