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- Title
P2Y<sub>2</sub>R activation by nucleotides promotes skin wound-healing process.
- Authors
Jin, Hana; Seo, Jihye; Eun, So Young; Joo, Young Nak; Park, Sang Won; Lee, Jae Heun; Chang, Ki Churl; Kim, Hye Jung
- Abstract
P2Y2R 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 P2Y2R in the wound-healing process and the mechanisms by which P2Y2R activation promotes wound healing in fibroblasts. The role of P2Y2R in skin wound healing was examined using a full-thickness skin wound model in wildtype (WT) and P2Y2R−/− mice and an in vitro scratch wound model in control or P2Y2R siRNA-transfected fibroblasts. WT mice showed significantly decreased wound size compared with P2Y2R−/− 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 P2Y2R−/− mice. Scratch-wounded fibroblasts increased ATP release, which peaked at 5 min. In addition, scratch wounding increased the level of P2Y2R mRNA. Activation of P2Y2R by ATP or UTP enhanced proliferation and migration of fibroblasts in in vitro scratch wound assays and were blocked by P2Y2R siRNA. Finally, ATP or UTP also increased the levels of ECM-related proteins through the activation of P2Y2R in fibroblasts. This study suggests that P2Y2R may be a potential therapeutic target to promote wound healing in chronic wound diseases.
- Subjects
CELL migration; EXTRACELLULAR matrix; NUCLEOTIDES; WOUND healing; ADENOSINE diphosphate; FIBROBLASTS; LABORATORY mice
- Publication
Experimental Dermatology, 2014, Vol 23, Issue 7, p480
- ISSN
0906-6705
- Publication type
Article
- DOI
10.1111/exd.12440