{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:49:23Z","timestamp":1793386163680,"version":"4.5.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012669","name":"Natural Science Foundation Project of Chongqing, Chongqing Science and Technology Commission","doi-asserted-by":"publisher","award":["CSTB2023NSCQ-MSX0639, CSTB2023NSCQ-MSX0817, CSTB2023NSCQ-MSX1061"],"award-info":[{"award-number":["CSTB2023NSCQ-MSX0639, CSTB2023NSCQ-MSX0817, CSTB2023NSCQ-MSX1061"]}],"id":[{"id":"10.13039\/501100012669","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301244"],"award-info":[{"award-number":["82301244"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Choroidal neovascularization (CNV) represents the predominant form of advanced wet Age-related Macular Degeneration (wAMD). Macrophages play a pivotal role in the pathological progression of CNV. Meteorin-like (Metrnl), a novel cytokine known for its anti-inflammatory properties in macrophages, is the focus of our investigation into its mechanism of action and its potential to impede CNV progression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Cell viability was evaluated through CCK-8 and EdU assays following Metrnl treatment. Expression levels of inflammatory cytokines and proteins were assessed using quantitative reverse\u2010transcription polymerase chain reaction(qRT\u2010PCR), enzyme-linked immunosorbent assay (ELISA), and western blot techniques. Protein-protein interactions were identified through protein mass spectrometry and co-immunoprecipitation (Co\u2010IP). Additionally, <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> neovascularization models were employed to evaluate angiogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results revealed downregulated Metrnl levels in the choroid-sclera complex of CNV mice, the aqueous humor of wAMD patients, and activated macrophages. Metrnl overexpression demonstrated a reduction in pro-inflammatory cytokine production, influenced endothelial cell function, and suppressed angiogenesis in choroid explants and CNV models. Through protein mass spectrometry and Co\u2010IP, we confirmed Metrnl binds to UCHL-1 to modulate the NF-\u03baB signaling pathway. This interaction inhibited the transcription and expression of pro-inflammatory cytokines, ultimately suppressing angiogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In summary, our findings indicate that Metrnl down-regulates macrophage pro-inflammatory cytokine secretion via the UCHL-1\/NF-\u03baB signaling pathway. This mechanism alleviates the inflammatory microenvironment and effectively inhibits choroidal neovascularization.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1379586","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T04:24:01Z","timestamp":1714451041000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Metrnl inhibits choroidal neovascularization by attenuating the choroidal inflammation via inactivating the UCHL-1\/NF-\u03baB signaling 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