title: The Retinoid Agonist Tazarotene Promotes Angiogenesis and Wound Healing.
abstract: Therapeutic angiogenesis is a major goal of regenerative medicine, but no clinically approved small molecule exists that enhances new blood vessel formation. Here we show, using a phenotype-driven high-content imaging screen of an annotated chemical library of 1,280 bioactive small molecules, that the retinoid agonist Tazarotene, enhances in vitro angiogenesis, promoting branching morphogenesis, and tubule remodeling. The proangiogenic phenotype is mediated by retinoic acid receptor but not retinoic X receptor activation, and is characterized by secretion of the proangiogenic factors hepatocyte growth factor, vascular endothelial growth factor, plasminogen activator, urokinase and placental growth factor, and reduced secretion of the antiangiogenic factor pentraxin-3 from adjacent fibroblasts. In vivo, Tazarotene enhanced the growth of mature and functional microvessels in Matrigel implants and wound healing models, and increased blood flow. Notably, in ear punch wound healing model, Tazarotene promoted tissue repair characterized by rapid ear punch closure with normal-appearing skin containing new hair follicles, and maturing collagen fibers. Our study suggests that Tazarotene, an FDA-approved small molecule, could be potentially exploited for therapeutic applications in neovascularization and wound healing.
authors.affiliation: Wellcome Trust Centre For Human Genetics, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.|BHF Centre of Research Excellence, University of Oxford, Oxford, UK.
authors.forename: Ayman
authors.initials: A
authors.lastname: Al Haj Zen
authors.affiliation: Wellcome Trust Centre For Human Genetics, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Dorota A
authors.initials: DA
authors.lastname: Nawrot
authors.affiliation: Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Howarth
authors.affiliation: University/BHF Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Caporali
authors.affiliation: Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ebner
authors.affiliation: Wellcome Trust Centre For Human Genetics, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Aude
authors.initials: A
authors.lastname: Vernet
authors.affiliation: Wellcome Trust Centre For Human Genetics, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Jurgen E
authors.initials: JE
authors.lastname: Schneider
authors.affiliation: Wellcome Trust Centre For Human Genetics, Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
authors.forename: Shoumo
authors.initials: S
authors.lastname: Bhattacharya
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051379:Mice; D009539:Nicotinic Acids / Q000008:administration & dosage* / Q000494:pharmacology; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D015398:Signal Transduction; D014945:Wound Healing / Q000187:drug effects*; D012176:Retinoids
chemical_list: D043925:Angiogenesis Inducing Agents; D009539:Nicotinic Acids; D018168:Receptors, Retinoic Acid; C086827:tazarotene; D012176:Retinoids