{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T02:01:17Z","timestamp":1790128877968,"version":"4.0.1"},"reference-count":101,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Universities and Research","award":["2022FYBMEX"],"award-info":[{"award-number":["2022FYBMEX"]}]},{"name":"\u201cA. Meyer\u201d University Children\u2019s Hospital","award":["2022FYBMEX"],"award-info":[{"award-number":["2022FYBMEX"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>\u03b2-adrenoceptors (BARs) are involved in vascular endothelial growth factor (VEGF) production during retinal neovascularization. Here, using human retinal endothelial and M\u00fcller cells (hRECs and MIO-M1, respectively), we evaluated the effects exerted by hypoxia on BARs, hypoxia-inducible factor-1\u03b1 subunit (HIF-1\u03b1) and VEGF, as well as the involvement of BAR3 and nitric oxide synthase (NOS) enzymes in hypoxia-induced VEGF production. We altered oxygen availability through a hypoxic incubator. BARs, HIF-1 \u03b1 and VEGF levels were evaluated. Cells were treated with the BAR3 antagonist SR59230A, different NOS inhibitors or the NO donor SNAP. The influence of the BAR3\/NOS axis on hypoxic VEGF production was assessed. Hypoxia upregulated BAR3, HIF-1\u03b1 and VEGF in hRECs and MIO-M1 cells. SR59230A counteracted hypoxia-dependent VEGF increase in both cell lines, exerting no effect on HIF-1\u03b1 upregulation. Treatments with NOS inhibitors prevented the hypoxia-dependent VEGF increase, while SNAP abrogated the effect of SR59230A in reducing hypoxia-induced VEGF upregulation. The present results corroborate the hypothesis that in the hypoxic retina, BAR3 influence on VEGF production is mediated by NO and suggest that, at least in endothelial and M\u00fcller cells, BAR3 activity is necessary to allow the HIF-1-mediated VEGF upregulation.<\/jats:p>","DOI":"10.3390\/ijms26094043","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T11:44:52Z","timestamp":1745495092000},"page":"4043","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Hypoxia-Dependent Upregulation of VEGF Relies on \u03b23-Adrenoceptor Signaling in Human Retinal Endothelial and M\u00fcller Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8825-142X","authenticated-orcid":false,"given":"Martina","family":"Lucchesi","sequence":"first","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1764-7025","authenticated-orcid":false,"given":"Lorenza","family":"Di Marsico","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8335-4821","authenticated-orcid":false,"given":"Lorenzo","family":"Guidotti","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8528-4094","authenticated-orcid":false,"given":"Matteo","family":"Lulli","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences \u201cMario Serio\u201d, University of Florence, 50121 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5310-9147","authenticated-orcid":false,"given":"Luca","family":"Filippi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Division of Neonatology and NICU, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0730-2648","authenticated-orcid":false,"given":"Silvia","family":"Marracci","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5181-4456","authenticated-orcid":false,"given":"Massimo","family":"Dal Monte","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3727\/096504010X12828372551867","article-title":"\u03b2-adrenergic receptors in cancer: Therapeutic implications","volume":"19","author":"Diz","year":"2010","journal-title":"Oncol. 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