{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:06:47Z","timestamp":1790467607598,"version":"4.1.0"},"reference-count":42,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,1,31]]},"abstract":"<jats:p>Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibroblast activation and fibrosis of the skin and internal organs. Alterations in cell\u2013integrin interaction are sufficient to initiate profibrotic processes. SSc fibroblasts express both \u03b1v\u03b23 and \u03b1v\u03b25 integrins and their activation induces myofibroblasts differentiation. The aim of the present study was to evaluate the effect of the anb3 and anb5 inhibitor, cilengitide, on the development of vascular and fibrotic changes in the chronic oxidant stress murine model of systemic sclerosis. SSc was induced in BALB\/c mice by daily s.c. injections of HOCl for 6 weeks. Mice were randomized in three arms: HOCl alone (n=8), HOCl + Cilengitide (n=8), or Vehicle alone (n=8). Treatment with cilengitide 20 (mg\/kg\/i.p.\/day) was started 4 weeks after the first administration of HOCl and maintained throughout the remaining experimental period (2 weeks). Lung, skin, and heart fibrosis were evaluated by histology while kidney morphology by PAS staining. Collagen type I, focal adhesion kinase (FAK), and a-SMA were evaluated by immunostaining and p-FAK and TGF-\u03b21 by Western blot and gene expression. Both cutaneous and pulmonary fibrosis induced by HOCl were attenuated by cilengitide treatment. Cilengitide administration reduced a-SMA, TGF-\u03b21, and p-FAK expression and the increased deposition of fibrillar collagen in the heart and prevented glomeruli collapse in the kidneys. The inhibition of a\u03bd\u03b23 and a\u03bd\u03b25 integrin signaling prevented systemic fibrosis and renal vascular abnormalities in the reactive oxygen species model of SSc. Integrins a\u03bd\u03b23 and a\u03bd\u03b25 could prove useful as a therapeutic target in SSc.<\/jats:p>","DOI":"10.1042\/cs20171426","type":"journal-article","created":{"date-parts":[[2017,12,14]],"date-time":"2017-12-14T01:35:12Z","timestamp":1513215312000},"page":"231-242","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Dual \u03b1v\u03b23 and \u03b1v\u03b25 blockade attenuates fibrotic and vascular alterations in a murine model of systemic sclerosis"],"prefix":"10.1042","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7594-8520","authenticated-orcid":false,"given":"Gian\u00a0Luca","family":"Bagnato","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Irrera","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Pizzino","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William\u00a0Neal","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Louisville, Louisville, Kentucky, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfilippo","family":"Bagnato","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Pallio","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Vaccaro","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8868-0762","authenticated-orcid":false,"given":"Francesco","family":"Squadrito","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Saitta","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenica","family":"Altavilla","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences, Morphological and Functional Images, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Bitto","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2018,1,19]]},"reference":[{"key":"2021113011022455700_B1","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/nrrheum.2011.149","article-title":"Understanding fibrosis in systemic sclerosis: shifting paradigms, emerging opportunities","volume":"8","author":"Bhattacharyya","year":"2012","journal-title":"Nat. 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