{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:18:34Z","timestamp":1793035114894,"version":"4.5.0"},"reference-count":56,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T00:00:00Z","timestamp":1561680000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["RF-2011-02351158"],"award-info":[{"award-number":["RF-2011-02351158"]}]},{"name":"Kaleyde Pharmaceuticals AG"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Retinitis pigmentosa (RP) is characterized by progressive loss of vision due to photoreceptor degeneration leading to secondary inflammation. The urokinase\u2010type plasminogen activator (uPA) system contributes to retinal inflammation, but its role in RP is unknown. In the rd10 mouse model of RP, we addressed this question with the use of the peptide UPARANT designed to interact with the uPA system. UPARANT was systemically administered from post\u2010natal day (PD) 10 to PD30 when its efficacy in RP rescue was investigated using electroretinographic recordings, Western blot and immunocytochemistry. Temporal profile of protein expression in the uPA system was also investigated. UPARANT reduced both M\u00fcller cell gliosis and up\u2010regulated levels of inflammatory markers and exerted major anti\u2010apoptotic effects without influencing the autophagy cascade. Rescue from retinal cell degeneration was accompanied by improved retinal function. No scotopic phototransduction was rescued in the UPARANT\u2010treated animals as determined by the kinetic analysis of rod\u2010mediated a\u2010waves and confirmed by rod photoreceptor markers. In contrast, the cone photopic b\u2010wave was recovered and its rescue was confirmed in the whole mounts using cone arrestin antibody. Investigation of the uPA system regulation over RP progression revealed extremely low levels of uPA and its receptor uPAR both of which were recovered by HIF\u20101\u03b1 stabilization indicating that HIF\u20101 regulates the expression of the uPA\/uPAR gene in the retina. Ameliorative effects of UPARANT were likely to occur through an inhibitory action on up\u2010regulated activity of the \u03b1v\u03b23 integrin\/Rac1 pathway that was suggested as a novel target for the development of therapeutic approaches against RP.<\/jats:p>","DOI":"10.1111\/jcmm.14391","type":"journal-article","created":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T13:59:36Z","timestamp":1561730376000},"page":"5176-5192","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["The urokinase\u2010type plasminogen activator system as drug target in retinitis pigmentosa: New pre\u2010clinical evidence in the rd10 mouse model"],"prefix":"10.1111","volume":"23","author":[{"given":"Maurizio","family":"Cammalleri","sequence":"first","affiliation":[{"name":"Department of Biology University of Pisa 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 Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo","family":"Locri","sequence":"additional","affiliation":[{"name":"Department of Biology University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Pecci","sequence":"additional","affiliation":[{"name":"Department of Biology University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"De Rosa","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine Second University of Napoli Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Pavone","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences University of Napoli Federico II Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Bagnoli","sequence":"additional","affiliation":[{"name":"Department of Biology University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,6,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-75402-4_23"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2012.07.006"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0000000000001542"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12428"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450120666181204164140"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-015-0159-6"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2018.08.005"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161211796718215"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2015.05.013"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.22356"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-18974"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-09-0174"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-13-0949"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-16323"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-18758"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-19909"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-016-4204-0"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-017-1051-5"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-21593"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/2904150"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14004"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0042-6989(01)00146-8"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07-9574LSF"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(00)00027-6"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.3006"},{"key":"e_1_2_10_27_1","first-page":"101","article-title":"Oxygen\u2010induced retinopathy in the mouse","volume":"35","author":"Smith LE","year":"1994","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019111"},{"key":"e_1_2_10_29_1","first-page":"2948","article-title":"Rod phototransduction in retinitis pigmentosa: estimation and interpretation of parameters derived from the rod a\u2010wave","volume":"35","author":"Hood DC","year":"1994","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.150400tc"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23243"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12805"},{"key":"e_1_2_10_33_1","first-page":"5176","article-title":"Autophagy: a role in the apoptosis, survival, inflammation, and development of the retina","volume":"25","author":"Lin W","year":"2018","journal-title":"Ophthalmic Res"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.06.011"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14613"},{"key":"e_1_2_10_36_1","first-page":"489","article-title":"Differential effect of the rd mutation on rods and cones in the mouse retina","volume":"17","author":"Carter\u2010Dawson LD","year":"1978","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2015.3812"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2015.4449"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.181329198"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2014.02.023"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.002534"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2014.203"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2018.01008"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2017.1358371"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-1549-8_7"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00098"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-22096"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.08.004"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00020"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700985R"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-017-0968-5"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-014-1274-4"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.202580"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aai8030"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201505298"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-13-0077"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1080\/08820538.2017.1388411"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcmm.14391","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.14391","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.14391","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.14391","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T08:39:21Z","timestamp":1697445561000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.14391"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,28]]},"references-count":56,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,8]]}},"alternative-id":["10.1111\/jcmm.14391"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.14391","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,28]]},"assertion":[{"value":"2019-01-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}