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Here, the expression, therapeutic effects and signalling mechanism of A<jats:sub>2A<\/jats:sub>R in corneal epithelial wound healing were investigated using the A<jats:sub>2A<\/jats:sub>R agonist CGS21680.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>A<jats:sub>2A<\/jats:sub>R localization and expression during wound healing in the murine cornea were determined by immunofluorescence staining, quantitative reverse transcription polymerase chain reaction (RT\u2010qPCR) and western blotting. The effect of CGS21680 on corneal epithelial wound healing in the lesioned corneal and cultured human corneal epithelial cells (hCECs) by modulating cellular proliferation and migration was critically evaluated. The role of Hippo\u2013YAP signalling in mediating the CGS21680 effect on wound healing by pharmacological inhibition of YAP signalling was explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>A<jats:sub>2A<\/jats:sub>R expression was up\u2010regulated after corneal epithelial injury. Topical administration of CGS21680 dose\u2010dependently promoted corneal epithelial wound healing in the injured corneal epithelium by promoting cellular proliferation. Furthermore, CGS21680 accelerated the cellular proliferation and migration of hCECs in vitro. A<jats:sub>2A<\/jats:sub>R activation promoted early up\u2010regulation and later down\u2010regulation of YAP signalling molecules, and pharmacological inhibition of YAP signalling reverted CGS21680\u2010mediated wound healing effect in vivo and in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>A<jats:sub>2A<\/jats:sub>R activation promotes wound healing by enhancing cellular proliferation and migration through the YAP signalling pathway. A<jats:sub>2A<\/jats:sub>Rs play an important role in the maintenance of corneal epithelium integrity and may represent a novel therapeutic target for facilitating corneal epithelial wound healing.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16468","type":"journal-article","created":{"date-parts":[[2024,6,15]],"date-time":"2024-06-15T08:15:10Z","timestamp":1718439310000},"page":"3779-3795","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["An agonist of the adenosine A<sub>2A<\/sub> receptor, CGS21680, promotes corneal epithelial wound healing via the YAP signalling pathway"],"prefix":"10.1111","volume":"181","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8158-3792","authenticated-orcid":false,"given":"Qiuqin","family":"Sun","sequence":"first","affiliation":[{"name":"The Molecular Neuropharmacology Laboratory and the Eye\u2010Brain Research Center, The State Key Laboratory of Ophthalmology, Optometry and Vision 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