title: Dopamine regulates mobilization of mesenchymal stem cells during wound angiogenesis.
abstract: Angiogenesis is an important step in the complex biological and molecular events leading to successful healing of dermal wounds. Among the different cellular effectors of wound angiogenesis, the role of mesenchymal stem cells (MSCs) is of current interest due to their transdifferentiation and proangiogenic potentials. Skin is richly innervated by sympathetic nerves which secrete dopamine (DA) and we have recently shown that concentration of DA present in synaptic cleft can significantly inhibit wound tissue neovascularization. As recent reports indicate that MSCs by mobilizing into wound bed play an important role in promoting wound angiogenesis, we therefore investigated the effect of DA on the migration of MSCs in wound tissues. DA acted through its D(2) receptors present in the MSCs to inhibit their mobilization to the wound beds by suppressing Akt phosphorylation and actin polymerization. In contrast, this inhibitory effect of DA was reversed after treatment with specific DA D(2) receptor antagonist. Increased mobilization of MSCs was demonstrated in the wound site following blockade of DA D(2) receptor mediated actions, and this in turn was associated with significantly more angiogenesis in wound tissues. This study is of translational value and indicates use of DA D(2) receptor antagonists to stimulate mobilization of these stem cells for faster regeneration of damaged tissues.
authors.affiliation: Department of Signal Transduction and Biogenic Amines, Chittaranjan National Cancer Institute, Kolkata, West Bengal, India.
authors.forename: Saurav
authors.initials: S
authors.lastname: Shome
authors.forename: Partha Sarathi
authors.initials: PS
authors.lastname: Dasgupta
authors.forename: Sujit
authors.initials: S
authors.lastname: Basu
mesh_terms: D000199:Actins / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D020405:Dermis / Q000098:blood supply / Q000187:drug effects* / Q000293:injuries; D004298:Dopamine / Q000494:pharmacology*; D015259:Dopamine Agents / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology*; D014947:Wounds and Injuries / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000199:Actins; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D034741:RNA, Small Interfering; D017448:Receptors, Dopamine D2; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt; D004298:Dopamine