title: P2Y2 R activation by nucleotides promotes skin wound-healing process.
abstract: P2Y2 R has been shown to be upregulated in a variety of tissues in response to stress or injury and to mediate tissue regeneration through its ability to activate multiple signalling pathways. This study aimed to investigate the role of P2Y2 R in the wound-healing process and the mechanisms by which P2Y2 R activation promotes wound healing in fibroblasts. The role of P2Y2 R in skin wound healing was examined using a full-thickness skin wound model in wildtype (WT) and P2Y2 R(-/-) mice and an in vitro scratch wound model in control or P2Y2 R siRNA-transfected fibroblasts. WT mice showed significantly decreased wound size compared with P2Y2 R(-/-) mice at day 14 post-wounding, and immunohistochemical analysis showed that a proliferation marker Ki67 and extracellular matrix (ECM)-related proteins VEGF, collagen I, fibronectin and α-SMA were overexpressed in WT mice, which were reduced in P2Y2 R(-/-) mice. Scratch-wounded fibroblasts increased ATP release, which peaked at 5 min. In addition, scratch wounding increased the level of P2Y2 R mRNA. Activation of P2Y2 R by ATP or UTP enhanced proliferation and migration of fibroblasts in in vitro scratch wound assays and were blocked by P2Y2 R siRNA. Finally, ATP or UTP also increased the levels of ECM-related proteins through the activation of P2Y2 R in fibroblasts. This study suggests that P2Y2 R may be a potential therapeutic target to promote wound healing in chronic wound diseases.
authors.affiliation: Department of Pharmacology, School of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju, Korea.
authors.forename: Hana
authors.initials: H
authors.lastname: Jin
authors.forename: Jihye
authors.initials: J
authors.lastname: Seo
authors.forename: So Young
authors.initials: SY
authors.lastname: Eun
authors.forename: Young Nak
authors.initials: YN
authors.lastname: Joo
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Park
authors.forename: Jae Heun
authors.initials: JH
authors.lastname: Lee
authors.forename: Ki Churl
authors.initials: KC
authors.lastname: Chang
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020868:Gene Silencing; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D034741:RNA, Small Interfering / Q000378:metabolism; D058473:Receptors, Purinergic P2Y2 / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D014544:Uridine Triphosphate / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing
chemical_list: D019394:Ki-67 Antigen; D034741:RNA, Small Interfering; D058473:Receptors, Purinergic P2Y2; D042461:Vascular Endothelial Growth Factor A; D000255:Adenosine Triphosphate; D003094:Collagen; D014544:Uridine Triphosphate
keywords: ECM-related genes; P2Y2 nucleotide receptor; cell migration; nucleotides; wound healing