{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T23:12:49Z","timestamp":1793747569561,"version":"4.6.1"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,15]],"date-time":"2017-08-15T00:00:00Z","timestamp":1502755200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,15]],"date-time":"2017-08-15T00:00:00Z","timestamp":1502755200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Angiogenesis as a pathological process in the eye can lead to blindness. In the cornea, suppression of angiogenesis by anti-VEGF treatment is only partially effective while steroids, although effective in treating inflammation and angiogenesis, have broad activity leading to undesirable side effects. In this study, genome-wide expression was investigated in a suture-induced corneal neovascularization model in rats, to investigate factors differentially targeted by dexamethasone and anti-<jats:italic>Vegf<\/jats:italic>. Topical treatment with either rat-specific anti-<jats:italic>Vegf<\/jats:italic>, dexamethasone, or normal goat IgG (sham) was given to sutured corneas for 48\u2009hours, after which <jats:italic>in vivo<\/jats:italic> imaging, tissue processing for RNA microarray, and immunofluorescence were performed. Dexamethasone suppressed limbal vasodilation (P\u2009&lt;\u20090.01) and genes in PI3K-Akt, focal adhesion, and chemokine signaling pathways more effectively than anti-<jats:italic>Vegf<\/jats:italic>. The most differentially expressed genes were confirmed by immunofluorescence, qRTPCR and Western blot. Strong suppression of <jats:italic>Reg3g<\/jats:italic> and the inflammatory chemokines <jats:italic>Ccl2<\/jats:italic> and <jats:italic>Cxcl5<\/jats:italic> and activation of classical complement pathway factors <jats:italic>C1r, C1s<\/jats:italic>, <jats:italic>C2<\/jats:italic>, and <jats:italic>C3<\/jats:italic> occurred with dexamethasone treatment, effects absent with anti-<jats:italic>Vegf<\/jats:italic> treatment. The genome-wide results obtained in this study provide numerous potential targets for specific blockade of inflammation and angiogenesis in the cornea not addressed by anti-<jats:italic>Vegf<\/jats:italic> treatment, as possible alternatives to broad-acting immunosuppressive therapy.<\/jats:p>","DOI":"10.1038\/s41598-017-07129-4","type":"journal-article","created":{"date-parts":[[2017,8,2]],"date-time":"2017-08-02T13:31:29Z","timestamp":1501680689000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Genome-wide expression differences in anti-Vegf and dexamethasone treatment of inflammatory angiogenesis in the rat cornea"],"prefix":"10.1038","volume":"7","author":[{"given":"Pierfrancesco","family":"Mirabelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9645-8942","authenticated-orcid":false,"given":"Anthony","family":"Mukwaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Lennikov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Xeroudaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Peebo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Schaupper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1079-4361","authenticated-orcid":false,"given":"Neil","family":"Lagali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,8,15]]},"reference":[{"key":"7129_CR1","doi-asserted-by":"publisher","first-page":"932","DOI":"10.1038\/nature04478","volume":"438","author":"P Carmeliet","year":"2005","unstructured":"Carmeliet, P. Angiogenesis in life, disease and medicine. Nature \n                           438, 932\u2013936, doi:10.1038\/nature04478 (2005).","journal-title":"Nature"},{"key":"7129_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1146\/annurev.med.57.121304.131306","volume":"57","author":"J Folkman","year":"2006","unstructured":"Folkman, J. Angiogenesis. Annual review of medicine \n                           57, 1\u201318, doi:10.1146\/annurev.med.57.121304.131306 (2006).","journal-title":"Annual review of medicine"},{"key":"7129_CR3","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1097\/00055735-200108000-00002","volume":"12","author":"JH Chang","year":"2001","unstructured":"Chang, J. H., Gabison, E. E., Kato, T. & Azar, D. T. Corneal neovascularization. Curr Opin Ophthalmol \n                           12, 242\u2013249 (2001).","journal-title":"Curr Opin Ophthalmol"},{"key":"7129_CR4","doi-asserted-by":"publisher","first-page":"1900","DOI":"10.1001\/jama.291.15.1900","volume":"291","author":"NM Bressler","year":"2004","unstructured":"Bressler, N. M. Age-related macular degeneration is the leading cause of blindness. JAMA \n                           291, 1900\u20131901 (2004).","journal-title":"JAMA"},{"key":"7129_CR5","doi-asserted-by":"publisher","first-page":"8","DOI":"10.2174\/157339909787314149","volume":"5","author":"TN Crawford","year":"2009","unstructured":"Crawford, T. N., Alfaro, D. V. 3rd, Kerrison, J. B. & Jablon, E. P. Diabetic retinopathy and angiogenesis. Current diabetes reviews \n                           5, 8\u201313 (2009).","journal-title":"Current diabetes reviews"},{"key":"7129_CR6","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1159\/000330174","volume":"100","author":"JC Rivera","year":"2011","unstructured":"Rivera, J. C. et al. Understanding retinopathy of prematurity: update on pathogenesis. Neonatology \n                           100, 343\u2013353, doi:10.1159\/000330174 (2011).","journal-title":"Neonatology"},{"key":"7129_CR7","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1055\/s-0032-1331569","volume":"229","author":"S Winterhalter","year":"2012","unstructured":"Winterhalter, S., Joussen, A. M., Pleyer, U. & Stubiger, N. [Inflammatory choroidal neovascularisations]. Klinische Monatsblatter fur Augenheilkunde \n                           229, 897\u2013904, doi:10.1055\/s-0032-1315249 (2012).","journal-title":"Klinische Monatsblatter fur Augenheilkunde"},{"key":"7129_CR8","doi-asserted-by":"publisher","first-page":"3","DOI":"10.2174\/1568010053622830","volume":"4","author":"A Naldini","year":"2005","unstructured":"Naldini, A. & Carraro, F. Role of inflammatory mediators in angiogenesis. Current drug targets. Inflammation and allergy \n                           4, 3\u20138 (2005).","journal-title":"Current drug targets. Inflammation and allergy"},{"key":"7129_CR9","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1042\/CS20040370","volume":"109","author":"H Takahashi","year":"2005","unstructured":"Takahashi, H. & Shibuya, M. The vascular endothelial growth factor (VEGF)\/VEGF receptor system and its role under physiological and pathological conditions. Clinical science \n                           109, 227\u2013241, doi:10.1042\/CS20040370 (2005).","journal-title":"Clinical science"},{"key":"7129_CR10","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1111\/j.1600-0420.1997.tb00623.x","volume":"75","author":"GB van Setten","year":"1997","unstructured":"van Setten, G. B. Vascular endothelial growth factor (VEGF) in normal human corneal epithelium: detection and physiological importance. Acta Ophthalmol Scand \n                           75, 649\u2013652 (1997).","journal-title":"Acta Ophthalmol Scand"},{"key":"7129_CR11","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1097\/ICO.0b013e31823f8b40","volume":"31","author":"ZR Li","year":"2012","unstructured":"Li, Z. R. et al. Activated macrophages induce neovascularization through upregulation of MMP-9 and VEGF in rat corneas. Cornea \n                           31, 1028\u20131035, doi:10.1097\/ICO.0b013e31823f8b40 (2012).","journal-title":"Cornea"},{"key":"7129_CR12","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/s00441-009-0908-5","volume":"339","author":"Y Gong","year":"2010","unstructured":"Gong, Y. & Koh, D. R. Neutrophils promote inflammatory angiogenesis via release of preformed VEGF in an in vivo corneal model. Cell Tissue Res \n                           339, 437\u2013448, doi:10.1007\/s00441-009-0908-5 (2010).","journal-title":"Cell Tissue Res"},{"key":"7129_CR13","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1002\/(SICI)1096-9896(200003)190:4<430::AID-PATH538>3.0.CO;2-6","volume":"190","author":"RD Leek","year":"2000","unstructured":"Leek, R. D. et al. Macrophage infiltration is associated with VEGF and EGFR expression in breast cancer. The Journal of pathology \n                           190, 430\u2013436, doi:10.1002\/(SICI)1096-9896(200003)190:4<430::AID-PATH538>3.0.CO;2-6 (2000).","journal-title":"The Journal of pathology"},{"key":"7129_CR14","doi-asserted-by":"publisher","first-page":"31189","DOI":"10.1074\/jbc.270.52.31189","volume":"270","author":"A Namiki","year":"1995","unstructured":"Namiki, A. et al. Hypoxia induces vascular endothelial growth factor in cultured human endothelial cells. The Journal of biological chemistry \n                           270, 31189\u201331195 (1995).","journal-title":"The Journal of biological chemistry"},{"key":"7129_CR15","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.exer.2014.06.006","volume":"125","author":"P Mirabelli","year":"2014","unstructured":"Mirabelli, P., Peebo, B. B., Xeroudaki, M., Koulikovska, M. & Lagali, N. Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model. Experimental eye research \n                           125, 118\u2013127 (2014).","journal-title":"Experimental eye research"},{"key":"7129_CR16","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.1056\/NEJMicm1005605","volume":"364","author":"DF Martin","year":"2011","unstructured":"Martin, D. F. et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med \n                           364, 1897\u20131908, doi:10.1056\/NEJMoa1102673 (2011).","journal-title":"N Engl J Med"},{"key":"7129_CR17","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.ophtha.2014.07.041","volume":"122","author":"K Berg","year":"2015","unstructured":"Berg, K., Pedersen, T. R., Sandvik, L. & Bragadottir, R. Comparison of ranibizumab and bevacizumab for neovascular age-related macular degeneration according to LUCAS treat-and-extend protocol. Ophthalmology \n                           122, 146\u2013152, doi:10.1016\/j.ophtha.2014.07.041 (2015).","journal-title":"Ophthalmology"},{"key":"7129_CR18","doi-asserted-by":"publisher","first-page":"51","DOI":"10.2174\/1381612043453603","volume":"10","author":"NC Ton","year":"2004","unstructured":"Ton, N. C. & Jayson, G. C. Resistance to anti-VEGF agents. Current pharmaceutical design \n                           10, 51\u201364 (2004).","journal-title":"Current pharmaceutical design"},{"key":"7129_CR19","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1016\/j.ejca.2010.02.020","volume":"46","author":"F Azam","year":"2010","unstructured":"Azam, F., Mehta, S. & Harris, A. L. Mechanisms of resistance to antiangiogenesis therapy. European journal of cancer \n                           46, 1323\u20131332, doi:10.1016\/j.ejca.2010.02.020 (2010).","journal-title":"European journal of cancer"},{"key":"7129_CR20","doi-asserted-by":"publisher","first-page":"3455","DOI":"10.1002\/cncr.26540","volume":"118","author":"SE Abdullah","year":"2012","unstructured":"Abdullah, S. E. & Perez-Soler, R. Mechanisms of resistance to vascular endothelial growth factor blockade. Cancer \n                           118, 3455\u20133467, doi:10.1002\/cncr.26540 (2012).","journal-title":"Cancer"},{"key":"7129_CR21","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.survophthal.2012.01.007","volume":"57","author":"JH Chang","year":"2012","unstructured":"Chang, J. H. et al. Corneal neovascularization: an anti-VEGF therapy review. Survey of ophthalmology \n                           57, 415\u2013429, doi:10.1016\/j.survophthal.2012.01.007 (2012).","journal-title":"Survey of ophthalmology"},{"key":"7129_CR22","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1001\/archophthalmol.2009.18","volume":"127","author":"MH Dastjerdi","year":"2009","unstructured":"Dastjerdi, M. H. et al. Topical bevacizumab in the treatment of corneal neovascularization: results of a prospective, open-label, noncomparative study. Arch Ophthalmol \n                           127, 381\u2013389, doi:10.1001\/archophthalmol.2009.18 (2009).","journal-title":"Arch Ophthalmol"},{"key":"7129_CR23","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1136\/bjophthalmol-2012-302137","volume":"97","author":"C Petsoglou","year":"2013","unstructured":"Petsoglou, C. et al. Subconjunctival bevacizumab induces regression of corneal neovascularisation: a pilot randomised placebo-controlled double-masked trial. The British journal of ophthalmology \n                           97, 28\u201332, doi:10.1136\/bjophthalmol-2012-302137 (2013).","journal-title":"The British journal of ophthalmology"},{"key":"7129_CR24","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1590\/S0004-27492012000400012","volume":"75","author":"AC Vieira","year":"2012","unstructured":"Vieira, A. C. et al. Intrastromal injection of bevacizumab in patients with corneal neovascularization. Arq Bras Oftalmol \n                           75, 277\u2013279 (2012).","journal-title":"Arq Bras Oftalmol"},{"key":"7129_CR25","doi-asserted-by":"publisher","first-page":"108","DOI":"10.3109\/02713680903429007","volume":"35","author":"I Avisar","year":"2010","unstructured":"Avisar, I., Weinberger, D. & Kremer, I. Effect of subconjunctival and intraocular bevacizumab injections on corneal neovascularization in a mouse model. Curr Eye Res \n                           35, 108\u2013115, doi:10.3109\/02713680903429007 (2010).","journal-title":"Curr Eye Res"},{"key":"7129_CR26","first-page":"104","volume":"17","author":"N Rocher","year":"2011","unstructured":"Rocher, N. et al. Effects of rat anti-VEGF antibody in a rat model of corneal graft rejection by topical and subconjunctival routes. Mol Vis \n                           17, 104\u2013112 (2011).","journal-title":"Mol Vis"},{"key":"7129_CR27","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1007\/s00417-009-1099-1","volume":"247","author":"Y Koenig","year":"2009","unstructured":"Koenig, Y. et al. Short- and long-term safety profile and efficacy of topical bevacizumab (Avastin) eye drops against corneal neovascularization. Graefes Arch Clin Exp Ophthalmol \n                           247, 1375\u20131382, doi:10.1007\/s00417-009-1099-1 (2009).","journal-title":"Graefes Arch Clin Exp Ophthalmol"},{"key":"7129_CR28","doi-asserted-by":"publisher","first-page":"221","DOI":"10.2174\/187221309789257450","volume":"3","author":"Y Shakiba","year":"2009","unstructured":"Shakiba, Y., Mansouri, K., Arshadi, D. & Rezaei, N. Corneal neovascularization: molecular events and therapeutic options. Recent patents on inflammation & allergy drug discovery \n                           3, 221\u2013231 (2009).","journal-title":"Recent patents on inflammation & allergy drug discovery"},{"key":"7129_CR29","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1001\/archopht.1953.00920020410004","volume":"49","author":"PR McDonald","year":"1953","unstructured":"McDonald, P. R., Leopold, I. H., Vogel, A. W. & Mulberger, R. D. Hydrocortisone (compound F) in ophthalmology; clinical and experimental studies. A.M.A. archives of ophthalmology \n                           49, 400\u2013412 (1953).","journal-title":"A.M.A. archives of ophthalmology"},{"key":"7129_CR30","doi-asserted-by":"publisher","first-page":"1904","DOI":"10.1016\/j.ophtha.2014.04.024","volume":"121","author":"DS Boyer","year":"2014","unstructured":"Boyer, D. S. et al. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology \n                           121, 1904\u20131914, doi:10.1016\/j.ophtha.2014.04.024 (2014).","journal-title":"Ophthalmology"},{"issue":"1134\u20131146","key":"7129_CR31","doi-asserted-by":"publisher","first-page":"e1133","DOI":"10.1016\/j.ophtha.2010.03.032","volume":"117","author":"JA Haller","year":"2010","unstructured":"Haller, J. A. et al. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology \n                           117(1134\u20131146), e1133, doi:10.1016\/j.ophtha.2010.03.032 (2010).","journal-title":"Ophthalmology"},{"key":"7129_CR32","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.exer.2014.06.006","volume":"125","author":"P Mirabelli","year":"2014","unstructured":"Mirabelli, P., Peebo, B. B., Xeroudaki, M., Koulikovska, M. & Lagali, N. Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model. Experimental eye research \n                           125, 118\u2013127, doi:10.1016\/j.exer.2014.06.006 (2014).","journal-title":"Experimental eye research"},{"key":"7129_CR33","doi-asserted-by":"publisher","first-page":"32137","DOI":"10.1038\/srep32137","volume":"6","author":"A Mukwaya","year":"2016","unstructured":"Mukwaya, A. et al. Factors regulating capillary remodeling in a reversible model of inflammatory corneal angiogenesis. Sci Rep \n                           6, 32137, doi:10.1038\/srep32137 (2016).","journal-title":"Sci Rep"},{"key":"7129_CR34","doi-asserted-by":"publisher","first-page":"3060","DOI":"10.1167\/iovs.10-6101","volume":"52","author":"BB Peebo","year":"2011","unstructured":"Peebo, B. B., Fagerholm, P., Traneus-R\u00f6ckert, C. & Lagali, N. Time-lapse in vivo imaging of corneal angiogenesis: the role of inflammatory cells in capillary sprouting. Investigative ophthalmology & visual science \n                           52, 3060\u20133068 (2011).","journal-title":"Investigative ophthalmology & visual science"},{"key":"7129_CR35","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1038\/nm.1985","volume":"15","author":"WW Kilarski","year":"2009","unstructured":"Kilarski, W. W., Samolov, B., Petersson, L., Kvanta, A. & Gerwins, P. Biomechanical regulation of blood vessel growth during tissue vascularization. Nature medicine \n                           15, 657\u2013664 (2009).","journal-title":"Nature medicine"},{"key":"7129_CR36","doi-asserted-by":"publisher","first-page":"3698","DOI":"10.4049\/jimmunol.175.6.3698","volume":"175","author":"M Honczarenko","year":"2005","unstructured":"Honczarenko, M., Ratajczak, M. Z., Nicholson-Weller, A. & Silberstein, L. E. Complement C3a enhances CXCL12 (SDF-1)-mediated chemotaxis of bone marrow hematopoietic cells independently of C3a receptor. J Immunol \n                           175, 3698\u20133706 (2005).","journal-title":"J Immunol"},{"key":"7129_CR37","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1038\/12431","volume":"5","author":"GJ del Zoppo","year":"1999","unstructured":"del Zoppo, G. J. In stroke, complement will get you nowhere. Nature medicine \n                           5, 995\u2013996 (1999).","journal-title":"Nature medicine"},{"key":"7129_CR38","doi-asserted-by":"publisher","first-page":"2420","DOI":"10.1016\/j.biomaterials.2013.11.079","volume":"35","author":"P Fagerholm","year":"2014","unstructured":"Fagerholm, P. et al. Stable corneal regeneration four years after implantation of a cell-free recombinant human collagen scaffold. Biomaterials \n                           35, 2420\u20132427, doi:10.1016\/j.biomaterials.2013.11.079 (2014).","journal-title":"Biomaterials"},{"key":"7129_CR39","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1007\/s10456-011-9223-3","volume":"14","author":"BB Peebo","year":"2011","unstructured":"Peebo, B. B., Fagerholm, P., Traneus-Rockert, C. & Lagali, N. Cellular level characterization of capillary regression in inflammatory angiogenesis using an in vivo corneal model. Angiogenesis \n                           14, 393\u2013405, doi:10.1007\/s10456-011-9223-3 (2011).","journal-title":"Angiogenesis"},{"key":"7129_CR40","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/nri3228","volume":"12","author":"RL Gallo","year":"2012","unstructured":"Gallo, R. L. & Hooper, L. V. Epithelial antimicrobial defence of the skin and intestine. Nature reviews. Immunology \n                           12, 503\u2013516, doi:10.1038\/nri3228 (2012).","journal-title":"Nature reviews. Immunology"},{"key":"7129_CR41","doi-asserted-by":"publisher","first-page":"3656","DOI":"10.1007\/s10620-015-3787-5","volume":"60","author":"G Yin","year":"2015","unstructured":"Yin, G. et al. Reg3g Promotes Pancreatic Carcinogenesis in a Murine Model of Chronic Pancreatitis. Dig Dis Sci \n                           60, 3656\u20133668, doi:10.1007\/s10620-015-3787-5 (2015).","journal-title":"Dig Dis Sci"},{"key":"7129_CR42","first-page":"4007","volume":"86","author":"EK Kruithof","year":"1995","unstructured":"Kruithof, E. K., Baker, M. S. & Bunn, C. Biological and clinical aspects of plasminogen activator inhibitor type 2. BLOOD-NEW YORK \n                           86, 4007\u20134024 (1995).","journal-title":"BLOOD-NEW YORK"},{"key":"7129_CR43","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/nrc2400","volume":"8","author":"DR Croucher","year":"2008","unstructured":"Croucher, D. R., Saunders, D. N., Lobov, S. & Ranson, M. Revisiting the biological roles of PAI2 (SERPINB2) in cancer. Nature Reviews Cancer \n                           8, 535\u2013545 (2008).","journal-title":"Nature Reviews Cancer"},{"key":"7129_CR44","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1002\/jlb.62.5.604","volume":"62","author":"A Walz","year":"1997","unstructured":"Walz, A., Schmutz, P., Mueller, C. & Schnyder-Candrian, S. Regulation and function of the CXC chemokine ENA-78 in monocytes and its role in disease. J Leukoc Biol \n                           62, 604\u2013611 (1997).","journal-title":"J Leukoc Biol"},{"key":"7129_CR45","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1161\/01.RES.0000149518.86865.3e","volume":"95","author":"A Schober","year":"2004","unstructured":"Schober, A. et al. Crucial role of the CCL2\/CCR2 axis in neointimal hyperplasia after arterial injury in hyperlipidemic mice involves early monocyte recruitment and CCL2 presentation on platelets. Circ Res \n                           95, 1125\u20131133, doi:10.1161\/01.RES.0000149518.86865.3e (2004).","journal-title":"Circ Res"},{"key":"7129_CR46","doi-asserted-by":"publisher","first-page":"927","DOI":"10.1097\/01.LAB.0000075642.11787.83","volume":"83","author":"S Yoshida","year":"2003","unstructured":"Yoshida, S., Yoshida, A., Matsui, H., Takada, Y.-i & Ishibashi, T. Involvement of Macrophage Chemotactic Protein-1 and Interleukin-1\u03b2 During Inflammatory but Not Basic Fibroblast Growth Factor\u2013Dependent Neovascularization in the Mouse Cornea. Laboratory investigation \n                           83, 927\u2013938 (2003).","journal-title":"Laboratory investigation"},{"key":"7129_CR47","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1172\/JCI3145","volume":"102","author":"DA Arenberg","year":"1998","unstructured":"Arenberg, D. A. et al. Epithelial-neutrophil activating peptide (ENA-78) is an important angiogenic factor in non-small cell lung cancer. Journal of Clinical Investigation \n                           102, 465 (1998).","journal-title":"Journal of Clinical Investigation"},{"key":"7129_CR48","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/s10456-011-9227-z","volume":"14","author":"SR Pickens","year":"2011","unstructured":"Pickens, S. R. et al. Anti-CXCL5 therapy ameliorates IL-17-induced arthritis by decreasing joint vascularization. Angiogenesis \n                           14, 443\u2013455 (2011).","journal-title":"Angiogenesis"},{"key":"7129_CR49","doi-asserted-by":"publisher","first-page":"2651","DOI":"10.4049\/jimmunol.177.4.2651","volume":"177","author":"SM Stamatovic","year":"2006","unstructured":"Stamatovic, S. M., Keep, R. F., Mostarica-Stojkovic, M. & Andjelkovic, A. V. CCL2 regulates angiogenesis via activation of Ets-1 transcription factor. The Journal of Immunology \n                           177, 2651\u20132661 (2006).","journal-title":"The Journal of Immunology"},{"key":"7129_CR50","first-page":"937.934","volume":"23","author":"W Zhang","year":"2009","unstructured":"Zhang, W. et al. NADPH oxidase is critically involved in CCL2-induced endothelial cell activation. The FASEB Journal \n                           23, 937.934\u2013937.934 (2009).","journal-title":"The FASEB Journal"},{"key":"7129_CR51","doi-asserted-by":"publisher","first-page":"6853","DOI":"10.1038\/sj.onc.1203239","volume":"18","author":"HL Pahl","year":"1999","unstructured":"Pahl, H. L. Activators and target genes of Rel\/NF-kappaB transcription factors. Oncogene \n                           18, 6853\u20136866, doi:10.1038\/sj.onc.1203239 (1999).","journal-title":"Oncogene"},{"key":"7129_CR52","first-page":"2318","volume":"17","author":"JM Chen","year":"2013","unstructured":"Chen, J. M., Cui, X. P., Yao, X. D., Huang, L. H. & Xu, H. Molecular changes of mesenchymal stromal cells in response to dexamethasone treatment. Eur Rev Med Pharmacol Sci \n                           17, 2318\u20132322 (2013).","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"7129_CR53","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/j.1365-2249.1995.tb02290.x","volume":"101","author":"M Coulpier","year":"1995","unstructured":"Coulpier, M. et al. Activation of the endothelium by IL-1 alpha and glucocorticoids results in major increase of complement C3 and factor B production and generation of C3a. Clin Exp Immunol \n                           101, 142\u2013149 (1995).","journal-title":"Clin Exp Immunol"},{"key":"7129_CR54","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1001\/archotol.134.6.615","volume":"134","author":"A Neher","year":"2008","unstructured":"Neher, A. et al. Antimicrobial activity of dexamethasone and its combination with N-chlorotaurine. Archives of Otolaryngology\u2013Head & Neck Surgery \n                           134, 615\u2013620 (2008).","journal-title":"Archives of Otolaryngology\u2013Head & Neck Surgery"},{"key":"7129_CR55","first-page":"237","volume":"24","author":"RP Cleveland","year":"1983","unstructured":"Cleveland, R. P., Hazlett, L. D., Leon, M. A. & Berk, R. S. Role of complement in murine corneal infection caused by Pseudomonas aeruginosa. Invest Ophthalmol Vis Sci \n                           24, 237\u2013242 (1983).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"7129_CR56","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1001\/archopht.1982.01030030480022","volume":"100","author":"BJ Mondino","year":"1982","unstructured":"Mondino, B. J., Sundar-Raj, C. V. & Brady, K. J. Production of first component of complement by corneal fibroblasts in tissue culture. Arch Ophthalmol \n                           100, 478\u2013480 (1982).","journal-title":"Arch Ophthalmol"},{"key":"7129_CR57","first-page":"273","volume":"33","author":"C Verhagen","year":"1992","unstructured":"Verhagen, C., Breebaart, A. C. & Kijlstra, A. The effects of complement depletion on corneal inflammation in rats. Invest Ophthalmol Vis Sci \n                           33, 273\u2013279 (1992).","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"7129_CR58","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1159\/000219686","volume":"42","author":"A Machalinska","year":"2009","unstructured":"Machalinska, A. et al. Elevated plasma levels of C3a complement compound in the exudative form of age-related macular degeneration. Ophthalmic Res \n                           42, 54\u201359, doi:10.1159\/000219686 (2009).","journal-title":"Ophthalmic Res"},{"key":"7129_CR59","doi-asserted-by":"publisher","first-page":"491","DOI":"10.4049\/jimmunol.174.1.491","volume":"174","author":"PS Bora","year":"2005","unstructured":"Bora, P. S. et al. Role of complement and complement membrane attack complex in laser-induced choroidal neovascularization. J Immunol \n                           174, 491\u2013497 (2005).","journal-title":"J Immunol"},{"key":"7129_CR60","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1126\/science.1110359","volume":"308","author":"JL Haines","year":"2005","unstructured":"Haines, J. L. et al. Complement factor H variant increases the risk of age-related macular degeneration. Science \n                           308, 419\u2013421, doi:10.1126\/science.1110359 (2005).","journal-title":"Science"},{"key":"7129_CR61","doi-asserted-by":"publisher","first-page":"435607","DOI":"10.1155\/2013\/435607","volume":"2013","author":"F Parmeggiani","year":"2013","unstructured":"Parmeggiani, F. et al. Mechanism of inflammation in age-related macular degeneration: an up-to-date on genetic landmarks. Mediators of inflammation \n                           2013, 435607, doi:10.1155\/2013\/435607 (2013).","journal-title":"Mediators of inflammation"},{"key":"7129_CR62","doi-asserted-by":"publisher","first-page":"265","DOI":"10.21037\/atm.2016.06.26","volume":"4","author":"I Kourtzelis","year":"2016","unstructured":"Kourtzelis, I. & Rafail, S. The dual role of complement in cancer and its implication in anti-tumor therapy. Annals of translational medicine \n                           4, 265, doi:10.21037\/atm.2016.06.26 (2016).","journal-title":"Annals of translational medicine"},{"key":"7129_CR63","doi-asserted-by":"publisher","first-page":"4395","DOI":"10.1182\/blood-2010-01-261503","volume":"116","author":"HF Langer","year":"2010","unstructured":"Langer, H. F. et al. Complement-mediated inhibition of neovascularization reveals a point of convergence between innate immunity and angiogenesis. Blood \n                           116, 4395\u20134403, doi:10.1182\/blood-2010-01-261503 (2010).","journal-title":"Blood"},{"key":"7129_CR64","doi-asserted-by":"publisher","first-page":"3171","DOI":"10.1096\/fj.14-251041","volume":"28","author":"JH Sweigard","year":"2014","unstructured":"Sweigard, J. H. et al. The alternative complement pathway regulates pathological angiogenesis in the retina. FASEB journal: official publication of the Federation of American Societies for Experimental Biology \n                           28, 3171\u20133182, doi:10.1096\/fj.14-251041 (2014).","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"key":"7129_CR65","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1096\/fj.15-280834","volume":"30","author":"C Kim","year":"2016","unstructured":"Kim, C. et al. The alternative complement pathway aids in vascular regression during the early stages of a murine model of proliferative retinopathy. FASEB journal: official publication of the Federation of American Societies for Experimental Biology \n                           30, 1300\u20131305, doi:10.1096\/fj.15-280834 (2016).","journal-title":"FASEB journal: official publication of the Federation of American Societies for Experimental Biology"},{"key":"7129_CR66","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1038\/nbt1342","volume":"25","author":"D Ricklin","year":"2007","unstructured":"Ricklin, D. & Lambris, J. D. Complement-targeted therapeutics. Nature biotechnology \n                           25, 1265\u20131275, doi:10.1038\/nbt1342 (2007).","journal-title":"Nature biotechnology"},{"key":"7129_CR67","doi-asserted-by":"crossref","unstructured":"Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal of the Royal Statistical Society. Series B (Methodological), 289\u2013300 (1995).","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"7129_CR68","doi-asserted-by":"crossref","unstructured":"Szklarczyk, D. et al. STRING v10: protein\u2013protein interaction networks, integrated over the tree of life. Nucleic acids research, gku1003 (2014).","DOI":"10.1093\/nar\/gku1003"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07129-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07129-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07129-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T08:17:02Z","timestamp":1671783422000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07129-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,15]]},"references-count":68,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["7129"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-07129-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,15]]},"assertion":[{"value":"10 November 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 August 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"7616"}}