{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:29:43Z","timestamp":1791408583166,"version":"4.3.3"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"Foundation for Science and Technology","award":["Doctoral research fellowship 2020.04811"],"award-info":[{"award-number":["Doctoral research fellowship 2020.04811"]}]},{"name":"Foundation for Science and Technology","award":["CIBB (Center for Innovative Biomedicine and Biotechnology) research unit (UIDB\/04539\/Base\/2020 and UIDP\/04539\/Programatico\/2020)"],"award-info":[{"award-number":["CIBB (Center for Innovative Biomedicine and Biotechnology) research unit (UIDB\/04539\/Base\/2020 and UIDP\/04539\/Programatico\/2020)"]}]},{"name":"Global Ophthalmology Awards Program (GOAP)\/ Bayer"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Commun Signal"],"DOI":"10.1186\/s12964-025-02587-0","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T11:20:24Z","timestamp":1766402424000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Retinal pigment epithelium-derived extracellular vesicles mediate outer blood retinal barrier disruption in response to AMD-related stress"],"prefix":"10.1186","volume":"23","author":[{"given":"Beatriz","family":"Martins","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Boia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Correia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Ribeiro-Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Ramalho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f3nio Francisco","family":"Ambr\u00f3sio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrique","family":"Gir\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"issue":"2","key":"2587_CR1","doi-asserted-by":"publisher","first-page":"e106","DOI":"10.1016\/S2214-109X(13)70145-1","volume":"2","author":"WL Wong","year":"2014","unstructured":"Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106-16. https:\/\/doi.org\/10.1016\/S2214-109X(13)70145-1.","journal-title":"Lancet Glob Health."},{"issue":"3","key":"2587_CR2","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1016\/j.mcna.2021.01.003","volume":"105","author":"CJ Thomas","year":"2021","unstructured":"Thomas CJ, Mirza RG, Gill MK. Age-Related Macular Degeneration. Med Clin North Am. 2021;105(3):473\u201391. https:\/\/doi.org\/10.1016\/j.mcna.2021.01.003.","journal-title":"Med Clin North Am."},{"issue":"1","key":"2587_CR3","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.neuron.2012.06.018","volume":"75","author":"J Ambati","year":"2012","unstructured":"Ambati J, Fowler BJ. Mechanisms of age-related macular degeneration. Neuron. 2012;75(1):26\u201339. https:\/\/doi.org\/10.1016\/j.neuron.2012.06.018.","journal-title":"Neuron."},{"issue":"3","key":"2587_CR4","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1152\/physrev.00021.2004","volume":"85","author":"O Strauss","year":"2005","unstructured":"Strauss O. The retinal pigment epithelium in visual function. Physiol Rev. 2005;85(3):845\u201381. https:\/\/doi.org\/10.1152\/physrev.00021.2004.","journal-title":"Physiol Rev"},{"key":"2587_CR5","doi-asserted-by":"publisher","unstructured":"Martins B, Amorim M, Reis F, Ambrosio AF, Fernandes R. Extracellular vesicles and microrna: putative role in diagnosis and treatment of diabetic retinopathy. Antioxid (Basel). 2020;9(8). https:\/\/doi.org\/10.3390\/antiox9080705.","DOI":"10.3390\/antiox9080705"},{"issue":"1","key":"2587_CR6","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1186\/s12929-024-01036-3","volume":"31","author":"B Martins","year":"2024","unstructured":"Martins B, Pires M, Ambrosio AF, Girao H, Fernandes R. Contribution of extracellular vesicles for the pathogenesis of retinal diseases: shedding light on blood-retinal barrier dysfunction. J Biomed Sci. 2024;31(1):48. https:\/\/doi.org\/10.1186\/s12929-024-01036-3.","journal-title":"J Biomed Sci."},{"issue":"4","key":"2587_CR7","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/tra.12775","volume":"22","author":"F Colombo","year":"2021","unstructured":"Colombo F, Casella G, Podini P, et al. Polarized cells display asymmetric release of extracellular vesicles. Traffic. 2021;22(4):98\u2013110. https:\/\/doi.org\/10.1111\/tra.12775.","journal-title":"Traffic"},{"issue":"1","key":"2587_CR8","doi-asserted-by":"publisher","first-page":"4901","DOI":"10.1038\/s41598-017-05102-9","volume":"7","author":"M Klingeborn","year":"2017","unstructured":"Klingeborn M, Dismuke WM, Skiba NP, Kelly U, Stamer WD, Bowes Rickman C. Directional Exosome Proteomes Reflect Polarity-Specific Functions in Retinal Pigmented Epithelium Monolayers. Sci Rep. 2017;7(1):4901. https:\/\/doi.org\/10.1038\/s41598-017-05102-9.","journal-title":"Sci Rep."},{"issue":"4","key":"2587_CR9","doi-asserted-by":"publisher","first-page":"563","DOI":"10.4161\/auto.5.4.8163","volume":"5","author":"AL Wang","year":"2009","unstructured":"Wang AL, Lukas TJ, Yuan M, Du N, Tso MO, Neufeld AH. Autophagy, exosomes and drusen formation in age-related macular degeneration. Autophagy. 2009;5(4):563\u20134. https:\/\/doi.org\/10.4161\/auto.5.4.8163.","journal-title":"Autophagy."},{"issue":"8","key":"2587_CR10","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1111\/jcmm.12834","volume":"20","author":"S Atienzar-Aroca","year":"2016","unstructured":"Atienzar-Aroca S, Flores-Bellver M, Serrano-Heras G, et al. Oxidative stress in retinal pigment epithelium cells increases exosome secretion and promotes angiogenesis in endothelial cells. J Cell Mol Med. 2016;20(8):1457\u201366. https:\/\/doi.org\/10.1111\/jcmm.12834.","journal-title":"J Cell Mol Med"},{"issue":"11","key":"2587_CR11","doi-asserted-by":"publisher","first-page":"5244","DOI":"10.1111\/jcmm.13730","volume":"22","author":"S Atienzar-Aroca","year":"2018","unstructured":"Atienzar-Aroca S, Serrano-Heras G, Freire Valls A, et al. <article-title update=\"added\">Role of retinal pigment epithelium\u2010derived exosomes and autophagy in new blood vessel formation. J Cell Mol Med. 2018;22(11):5244\u201356. https:\/\/doi.org\/10.1111\/jcmm.13730.","journal-title":"J Cell Mol Med"},{"issue":"13","key":"2587_CR12","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12165","volume":"10","author":"M Flores-Bellver","year":"2021","unstructured":"Flores-Bellver M, Mighty J, Aparicio-Domingo S, et al. Extracellular vesicles released by human retinal pigment epithelium mediate increased polarised secretion of drusen proteins in response to AMD stressors. J Extracell Vesicles. 2021;10(13):e12165. https:\/\/doi.org\/10.1002\/jev2.12165.","journal-title":"J Extracell Vesicles"},{"issue":"12","key":"2587_CR13","doi-asserted-by":"publisher","first-page":"e12295","DOI":"10.1002\/jev2.12295","volume":"11","author":"M Kurzawa-Akanbi","year":"2022","unstructured":"Kurzawa-Akanbi M, Whitfield P, Burte F, et al. Retinal pigment epithelium extracellular vesicles are potent inducers of age-related macular degeneration disease phenotype in the outer retina. J Extracell Vesicles. 2022;11(12):e12295. https:\/\/doi.org\/10.1002\/jev2.12295.","journal-title":"J Extracell Vesicles."},{"key":"2587_CR14","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1007\/978-3-031-27681-1_4","volume":"1415","author":"B Martins","year":"2023","unstructured":"Martins B, Fernandes R. Disturbed matrix metalloproteinases activity in age-related macular degeneration. Adv Exp Med Biol. 2023;1415:21\u20136. https:\/\/doi.org\/10.1007\/978-3-031-27681-1_4.","journal-title":"Adv Exp Med Biol"},{"issue":"7","key":"2587_CR15","doi-asserted-by":"publisher","first-page":"4459","DOI":"10.1167\/iovs.10-6678","volume":"52","author":"AA Hussain","year":"2011","unstructured":"Hussain AA, Lee Y, Zhang JJ, Marshall J. Disturbed matrix metalloproteinase activity of Bruch\u2019s membrane in age-related macular degeneration. Invest Ophthalmol Vis Sci. 2011;52(7):4459\u201366. https:\/\/doi.org\/10.1167\/iovs.10-6678.","journal-title":"Invest Ophthalmol Vis Sci."},{"issue":"11","key":"2587_CR16","first-page":"2194","volume":"39","author":"B Steen","year":"1998","unstructured":"Steen B, Sejersen S, Berglin L, Seregard S, Kvanta A. Matrix metalloproteinases and metalloproteinase inhibitors in choroidal neovascular membranes. Invest Ophthalmol Vis Sci. 1998;39(11):2194\u2013200.","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"15","key":"2587_CR17","doi-asserted-by":"publisher","first-page":"2290","DOI":"10.1096\/fj.03-0113fje","volume":"17","author":"V Lambert","year":"2003","unstructured":"Lambert V, Wielockx B, Munaut C, et al. MMP\u20102 and MMP\u20109 synergize in promoting choroidal neovascularization. FASEB J. 2003;17(15):2290. https:\/\/doi.org\/10.1096\/fj.03-0113fje.","journal-title":"FASEB J"},{"key":"2587_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrep.2020.100760","volume":"22","author":"A Fukushima","year":"2020","unstructured":"Fukushima A, Takahashi E, Saruwatari J, Tanihara H, Inoue T. The angiogenic effects of exosomes secreted from retinal pigment epithelial cells on endothelial cells. Biochem Biophys Rep. 2020;22:100760. https:\/\/doi.org\/10.1016\/j.bbrep.2020.100760.","journal-title":"Biochem Biophys Rep"},{"key":"2587_CR19","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.mehy.2016.10.027","volume":"97","author":"Y Tong","year":"2016","unstructured":"Tong Y, Zhou YL, Wang YX, Zhao PQ, Wang ZY. Retinal pigment epithelium cell-derived exosomes: possible relevance to CNV in wet-age related macular degeneration. Med Hypotheses. 2016;97:98-101.10.1016\/j.mehy.2016.10.027.","journal-title":"Med Hypotheses"},{"issue":"11","key":"2587_CR20","doi-asserted-by":"publisher","first-page":"1338","DOI":"10.1093\/cvr\/cvx118","volume":"113","author":"TM Ribeiro-Rodrigues","year":"2017","unstructured":"Ribeiro-Rodrigues TM, Laundos TL, Pereira-Carvalho R, et al. Exosomes secreted by cardiomyocytes subjected to ischaemia promote cardiac angiogenesis. Cardiovasc Res. 2017;113(11):1338\u201350. https:\/\/doi.org\/10.1093\/cvr\/cvx118.","journal-title":"Cardiovasc Res"},{"issue":"4","key":"2587_CR21","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.2741\/481","volume":"4","author":"J Zhang","year":"2012","unstructured":"Zhang J, Xu G, Zhang L, et al. A modified histoimmunochemistry-assisted method for in situ RPE evaluation. Front Biosci (Elite Ed). 2012;4(4):1571. https:\/\/doi.org\/10.2741\/481.","journal-title":"Front Biosci (Elite Ed)"},{"issue":"9","key":"2587_CR22","doi-asserted-by":"publisher","first-page":"1454","DOI":"10.1016\/j.bbadis.2014.04.013","volume":"1842","author":"A Goncalves","year":"2014","unstructured":"Goncalves A, Marques C, Leal E, et al. Dipeptidyl peptidase-IV inhibition prevents blood-retinal barrier breakdown, inflammation and neuronal cell death in the retina of type 1 diabetic rats. Biochim Biophys Acta. 2014;1842(9):1454\u201363. https:\/\/doi.org\/10.1016\/j.bbadis.2014.04.013.","journal-title":"Biochim Biophys Acta"},{"key":"2587_CR23","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1007\/978-1-0716-2289-6_18","volume":"2492","author":"C Greene","year":"2022","unstructured":"Greene C, Campbell M. Immunohistochemical analysis of tight junction proteins. Methods Mol Biol. 2022;2492:307\u201314. https:\/\/doi.org\/10.1007\/978-1-0716-2289-6_18.","journal-title":"Methods Mol Biol"},{"issue":"4","key":"2587_CR24","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.1007\/s00429-016-1316-8","volume":"222","author":"G Tavares","year":"2017","unstructured":"Tavares G, Martins M, Correia JS, et al. Employing an open-source tool to assess astrocyte tridimensional structure. Brain Struct Funct. 2017;222(4):1989. https:\/\/doi.org\/10.1007\/s00429-016-1316-8.","journal-title":"Brain Struct Funct"},{"key":"2587_CR25","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/538737","volume":"2014","author":"C Marques","year":"2014","unstructured":"Marques C, Mega C, Goncalves A, et al. Sitagliptin prevents inflammation and apoptotic cell death in the kidney of type 2 diabetic animals. Mediators Inflamm. 2014;2014:538737.10.1155\/2014\/538737.","journal-title":"Mediators Inflamm"},{"key":"2587_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2021.108496","volume":"205","author":"Y Otsuki","year":"2021","unstructured":"Otsuki Y, Ito E, Mukai A, et al. CD63(+) extracellular vesicles from retinal pigment epithelial cells participate in crosstalk with macrophages in the innate inflammatory axis. Exp Eye Res. 2021;205:108496. https:\/\/doi.org\/10.1016\/j.exer.2021.108496.","journal-title":"Exp Eye Res"},{"issue":"10","key":"2587_CR27","doi-asserted-by":"publisher","first-page":"4101","DOI":"10.1167\/iovs.15-18353","volume":"57","author":"JE Knickelbein","year":"2016","unstructured":"Knickelbein JE, Liu B, Arakelyan A, et al. Modulation of immune responses by extracellular vesicles from retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2016;57(10):4101. https:\/\/doi.org\/10.1167\/iovs.15-18353.","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"22","key":"2587_CR28","doi-asserted-by":"publisher","first-page":"13324","DOI":"10.1111\/jcmm.15951","volume":"24","author":"Y Zhang","year":"2020","unstructured":"Zhang Y, Wang K, Pan J, et al. Exosomes mediate an epithelial-mesenchymal transition cascade in retinal pigment epithelial cells: implications for proliferative vitreoretinopathy. J Cell Mol Med. 2020;24(22):13324. https:\/\/doi.org\/10.1111\/jcmm.15951.","journal-title":"J Cell Mol Med"},{"issue":"1","key":"2587_CR29","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1002\/JLB.3MIA0321-150RR","volume":"111","author":"ML Willis","year":"2022","unstructured":"Willis ML, Mahung C, Wallet SM, et al. Plasma extracellular vesicles released after severe burn injury modulate macrophage phenotype and function. J Leukoc Biol. 2022;111(1):33\u201349. https:\/\/doi.org\/10.1002\/JLB.3MIA0321-150RR.","journal-title":"J Leukoc Biol."},{"key":"2587_CR30","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/978-3-319-17121-0_11","volume":"854","author":"W Ma","year":"2016","unstructured":"Ma W, Wong WT. Aging changes in retinal microglia and their relevance to age-related retinal disease. Adv Exp Med Biol. 2016;854:73.","journal-title":"Adv Exp Med Biol"},{"key":"2587_CR31","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.exer.2013.09.003","volume":"123","author":"S Fuhrmann","year":"2014","unstructured":"Fuhrmann S, Zou C, Levine EM. Retinal pigment epithelium development, plasticity, and tissue homeostasis. Exp Eye Res. 2014;123:141\u201350. https:\/\/doi.org\/10.1016\/j.exer.2013.09.003.","journal-title":"Exp Eye Res"},{"key":"2587_CR32","doi-asserted-by":"publisher","first-page":"1059141","DOI":"10.3389\/fcell.2023.1059141","volume":"11","author":"A Chatterjee","year":"2023","unstructured":"Chatterjee A, Singh R. Extracellular vesicles: an emerging player in retinal homeostasis. Front Cell Dev Biol. 2023;11:1059141. https:\/\/doi.org\/10.3389\/fcell.2023.1059141.","journal-title":"Front Cell Dev Biol"},{"issue":"12","key":"2587_CR33","first-page":"13227","volume":"13","author":"F Sun","year":"2021","unstructured":"Sun F, Xu W, Qian H. The emerging role of extracellular vesicles in retinal diseases. Am J Transl Res. 2021;13(12):13227\u201345.","journal-title":"Am J Transl Res"},{"key":"2587_CR34","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.exer.2013.02.012","volume":"110","author":"M Shirasawa","year":"2013","unstructured":"Shirasawa M, Sonoda S, Terasaki H, et al. TNF-\u03b1 disrupts morphologic and functional barrier properties of polarized retinal pigment epithelium. Exp Eye Res. 2013;110:59\u201369. https:\/\/doi.org\/10.1016\/j.exer.2013.02.012.","journal-title":"Exp Eye Res"},{"issue":"10","key":"2587_CR35","doi-asserted-by":"publisher","first-page":"1594","DOI":"10.18240\/ijo.2018.10.04","volume":"11","author":"XL Zou","year":"2018","unstructured":"Zou XL, Wang GF, Li DD, et al. Protection of tight junction between RPE cells with tissue factor targeting peptide. Int J Ophthalmol. 2018;11(10):1594\u20139. https:\/\/doi.org\/10.18240\/ijo.2018.10.04.","journal-title":"Int J Ophthalmol"},{"issue":"4","key":"2587_CR36","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1007\/s00417-011-1617-9","volume":"249","author":"I Sanchez","year":"2011","unstructured":"Sanchez I, Martin R, Ussa F, Fernandez-Bueno I. The parameters of the porcine eyeball. Graefes Arch Clin Exp Ophthalmol. 2011;249(4):475\u201382. https:\/\/doi.org\/10.1007\/s00417-011-1617-9.","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"2587_CR37","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.exer.2014.05.003","volume":"124","author":"KA Toops","year":"2014","unstructured":"Toops KA, Tan LX, Lakkaraju A. A detailed three-step protocol for live imaging of intracellular traffic in polarized primary porcine RPE monolayers. Exp Eye Res. 2014;124:74\u201385. https:\/\/doi.org\/10.1016\/j.exer.2014.05.003.","journal-title":"Exp Eye Res"},{"key":"2587_CR38","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21165934","author":"L Garcia-Onrubia","year":"2020","unstructured":"Garcia-Onrubia L, Valentin-Bravo FJ, Coco-Martin RM, et al. Matrix metalloproteinases in Age-Related Macular Degeneration (AMD). Int J Mol Sci. 2020. https:\/\/doi.org\/10.3390\/ijms21165934.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"2587_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-16701-6","volume":"12","author":"L Chen","year":"2022","unstructured":"Chen L, Perera ND, Karoukis AJ, et al. Oxidative stress differentially impacts apical and basolateral secretion of angiogenic factors from human iPSC-derived retinal pigment epithelium cells. Sci Rep. 2022;12(1):12694. https:\/\/doi.org\/10.1038\/s41598-022-16701-6.","journal-title":"Sci Rep"},{"key":"2587_CR40","doi-asserted-by":"publisher","DOI":"10.3390\/cells9051217","author":"CH Alves","year":"2020","unstructured":"Alves CH, Fernandes R, Santiago AR, Ambrosio AF. Microglia contribution to the regulation of the retinal and choroidal vasculature in Age-Related Macular Degeneration. Cells. 2020. https:\/\/doi.org\/10.3390\/cells9051217.","journal-title":"Cells"},{"key":"2587_CR41","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/978-1-4614-0631-0_6","volume":"723","author":"W Ma","year":"2012","unstructured":"Ma W, Zhao L, Wong WT. Microglia in the outer retina and their relevance to pathogenesis of age-related macular degeneration. Adv Exp Med Biol. 2012;723:37\u201342. https:\/\/doi.org\/10.1007\/978-1-4614-0631-0_6.","journal-title":"Adv Exp Med Biol"},{"issue":"1","key":"2587_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101523","volume":"298","author":"J Saada","year":"2022","unstructured":"Saada J, McAuley RJ, Marcatti M, Tang TZ, Motamedi M, Szczesny B. Oxidative stress induces Z-DNA-binding protein 1-dependent activation of microglia via mtDNA released from retinal pigment epithelial cells. J Biol Chem. 2022;298(1):101523. https:\/\/doi.org\/10.1016\/j.jbc.2021.101523.","journal-title":"J Biol Chem"}],"container-title":["Cell Communication and Signaling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12964-025-02587-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-025-02587-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12964-025-02587-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T20:55:01Z","timestamp":1767041701000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12964-025-02587-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,22]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2587"],"URL":"https:\/\/doi.org\/10.1186\/s12964-025-02587-0","relation":{},"ISSN":["1478-811X"],"issn-type":[{"value":"1478-811X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,22]]},"assertion":[{"value":"6 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"542"}}