{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T05:31:47Z","timestamp":1775626307860,"version":"3.50.1"},"reference-count":51,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,12,11]],"date-time":"2018-12-11T00:00:00Z","timestamp":1544486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The corneal endothelium is composed of a single hexagonal\u2010shaped cells layer adherent to the Descemet's membrane. The primary function of these cells is maintaining of tissue clarity by regulating its hydration. Trauma, aging or other pathologies cause their loss, counterbalanced by enlargement of survived cells unable to guarantee an efficient fluid pumping to and from the stroma. Regenerative medicine using human corneal endothelial cells (HCECs) isolated from peripheral corneal\u2010scleral tissue of a donor could be an attractive solution, overcoming transplantation problems. In a previous study, we have demonstrated that HCECs treatment with pituitary adenylate cyclase\u2013activating polypeptide (PACAP) following growth factors deprivation prevents their degeneration. However, the molecular mechanism mediating this effect has not been clarified, yet. Here, we have shown for the first time the expression of PACAP and its receptor (PAC1R) in human corneal endothelium and demonstrated that this peptide, selectively binding to PAC1R, induces epidermal growth factor receptor (EGFR) phosphorylation and the MAPK\/ERK1\/2 signaling pathway activation. In conclusion, our data have suggested that PACAP could represent an important trophic factor in maintaining human corneal endothelial integrity through EGFR transactivation. Therefore, PACAP, as well as epidermal growth factor and fibroblast growth factor, could co\u2010operate to guarantee tissue physiological functioning by supporting corneal endothelial barrier integrity.<\/jats:p>","DOI":"10.1002\/jcb.28293","type":"journal-article","created":{"date-parts":[[2018,12,12]],"date-time":"2018-12-12T06:40:23Z","timestamp":1544596823000},"page":"10097-10105","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["PACAP through EGFR transactivation preserves human corneal endothelial integrity"],"prefix":"10.1002","volume":"120","author":[{"given":"Grazia","family":"Maugeri","sequence":"first","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences Section of Human Anatomy and Histology University of Catania Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agata Grazia","family":"D'Amico","sequence":"additional","affiliation":[{"name":"Department of Human Science and Promotion of Quality of Life San Raffaele Open University of Rome Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Castrogiovanni","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences Section of Human Anatomy and Histology University of Catania Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvatore","family":"Saccone","sequence":"additional","affiliation":[{"name":"Department of Biological Geological and Environmental Sciences Section of Animal Biology University of Catania Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Concetta","family":"Federico","sequence":"additional","affiliation":[{"name":"Department of Biological Geological and Environmental Sciences Section of Animal Biology University of Catania Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Reibaldi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eye Clinic University of Catania Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eye Clinic University of Catania Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenza","family":"Bonfiglio","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eye Clinic University of Catania Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresio","family":"Avitabile","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eye Clinic University of Catania Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Longo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Eye Clinic University of Catania Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1114-8265","authenticated-orcid":false,"given":"Velia","family":"D'Agata","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences Section of Human Anatomy and Histology University of Catania Catania Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,12,11]]},"reference":[{"key":"e_1_2_5_1_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/02713689109001742"},{"key":"e_1_2_5_1_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.eye.6700559"},{"key":"e_1_2_5_1_4_1","first-page":"2152","article-title":"Mechanisms of mitotic inhibition in corneal endothelium: contact inhibition and TGF\u2010\u03b22","volume":"43","author":"Joyce NC","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_5_1_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ico.0000136666.63870.18"},{"key":"e_1_2_5_1_6_1","first-page":"2427","article-title":"Corneal endothelial modulation: bFGF as direct mediator and corneal endothelium modulation factor as inducer","volume":"35","author":"Kay EP","year":"1994","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_5_1_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3182111f01"},{"key":"e_1_2_5_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2017.11.003"},{"key":"e_1_2_5_1_9_1","doi-asserted-by":"publisher","DOI":"10.2170\/jjphysiol.48.301"},{"key":"e_1_2_5_1_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1996.tb17505.x"},{"key":"e_1_2_5_1_11_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.109.001370"},{"key":"e_1_2_5_1_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12565-016-0351-0"},{"key":"e_1_2_5_1_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-012-9755-z"},{"key":"e_1_2_5_1_14_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161211795589355"},{"key":"e_1_2_5_1_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms16035922"},{"key":"e_1_2_5_1_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25899"},{"issue":"7","key":"e_1_2_5_1_17_1","first-page":"139","article-title":"PACAP and VIP inhibit the invasiveness of glioblastoma cells exposed to hypoxia through the regulation of HIFs and EGFR expression","volume":"31","author":"Maugeri G","year":"2016","journal-title":"Front Pharmacol"},{"key":"e_1_2_5_1_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.npep.2018.04.009"},{"key":"e_1_2_5_1_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000218"},{"key":"e_1_2_5_1_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2013.11.003"},{"key":"e_1_2_5_1_21_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17088"},{"key":"e_1_2_5_1_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12034"},{"key":"e_1_2_5_1_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-015-0621-7"},{"key":"e_1_2_5_1_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25510"},{"key":"e_1_2_5_1_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25616"},{"key":"e_1_2_5_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2012.11.015"},{"key":"e_1_2_5_1_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-015-0505-x"},{"key":"e_1_2_5_1_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601608"},{"key":"e_1_2_5_1_29_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.190033"},{"key":"e_1_2_5_1_30_1","doi-asserted-by":"publisher","DOI":"10.1159\/000101926"},{"key":"e_1_2_5_1_31_1","first-page":"1346","article-title":"Activation of epidermal growth factor receptor during corneal epithelial migration","volume":"41","author":"Zieske JD","year":"2000","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_5_1_32_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.32.19666"},{"key":"e_1_2_5_1_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-01-00083.1997"},{"key":"e_1_2_5_1_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2014.51"},{"key":"e_1_2_5_1_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-014-0335-2"},{"key":"e_1_2_5_1_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-016-0869-6"},{"key":"e_1_2_5_1_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2017.09.014"},{"key":"e_1_2_5_1_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25971"},{"key":"e_1_2_5_1_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2013.05.006"},{"key":"e_1_2_5_1_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(93)90018-B"},{"key":"e_1_2_5_1_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90025-6"},{"key":"e_1_2_5_1_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(94)91825-2"},{"key":"e_1_2_5_1_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(95)00258-K"},{"key":"e_1_2_5_1_44_1","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1994.1152"},{"key":"e_1_2_5_1_45_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.106.1.145"},{"key":"e_1_2_5_1_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-012-9812-7"},{"key":"e_1_2_5_1_47_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-1139"},{"key":"e_1_2_5_1_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ico.0000214224.90743.01"},{"key":"e_1_2_5_1_49_1","first-page":"2079","article-title":"Distribution of very late activation integrins in the human cornea. An immunohistochemical study using monoclonal antibodies","volume":"32","author":"Lauweryns B","year":"1991","journal-title":"Invest Ophthalmol Vis Sci"},{"issue":"7","key":"e_1_2_5_1_50_1","first-page":"589","article-title":"The endothelial pump of the cornea","volume":"16","author":"Hodson S","year":"1977","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"e_1_2_5_1_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)00055-X"},{"key":"e_1_2_5_1_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27328"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.28293","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.28293","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcb.28293","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.28293","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,3]],"date-time":"2024-05-03T07:43:26Z","timestamp":1714722206000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.28293"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,11]]},"references-count":51,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1002\/jcb.28293"],"URL":"https:\/\/doi.org\/10.1002\/jcb.28293","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,11]]},"assertion":[{"value":"2018-08-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}