Systemic sclerosis (SSc) is a connective tissue disorder characterized by fibroblast activation and fibrosis of the skin and internal organs. Alterations in cell–integrin interaction are sufficient to initiate profibrotic processes. SSc fibroblasts express both αvβ3 and αvβ5 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-β1 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-β1, and p-FAK expression and the increased deposition of fibrillar collagen in the heart and prevented glomeruli collapse in the kidneys. The inhibition of aνβ3 and aνβ5 integrin signaling prevented systemic fibrosis and renal vascular abnormalities in the reactive oxygen species model of SSc. Integrins aνβ3 and aνβ5 could prove useful as a therapeutic target in SSc.
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January 2018
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Oleic-acid-treated HepG2 cells immunostained for PGC-1α (PPARγ co-activator-1 α). In Clinical Science volume 132, issue 1, the results of work by Bernardi et al. include reporting that the protein TRAIL (TNF-related apoptosis inducing ligand) increases the expression of PGC-1α in HepG2 cells cultured with oleic acid. Overall, the article points to a potential therapeutic role for TRAIL against impaired glucose tolerance and non-alcoholic fatty liver disease; for details see pages 69–83.
Research Article|
January 19 2018
Dual αvβ3 and αvβ5 blockade attenuates fibrotic and vascular alterations in a murine model of systemic sclerosis
Gian Luca Bagnato
;
Gian Luca Bagnato
*
1Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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Natasha Irrera;
Natasha Irrera
*
1Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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Gabriele Pizzino;
Gabriele Pizzino
*
1Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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Domenico Santoro;
Domenico Santoro
1Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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William Neal Roberts;
William Neal Roberts
2Department of Medicine, University of Louisville, Louisville, Kentucky, U.S.A.
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Gianfilippo Bagnato;
Gianfilippo Bagnato
1Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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Giovanni Pallio;
Giovanni Pallio
1Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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Mario Vaccaro;
Mario Vaccaro
1Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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Francesco Squadrito
;
Francesco Squadrito
1Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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Antonino Saitta;
Antonino Saitta
1Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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Domenica Altavilla;
Domenica Altavilla
3Department of Biomedical and Dental Sciences, Morphological and Functional Images, University of Messina, Messina, Italy
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Alessandra Bitto
1Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Correspondence: Alessandra Bitto ([email protected])
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Publisher: Portland Press Ltd
Received:
October 12 2017
Revision Received:
December 06 2017
Accepted:
December 12 2017
Accepted Manuscript online:
December 13 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (2): 231–242.
Article history
Received:
October 12 2017
Revision Received:
December 06 2017
Accepted:
December 12 2017
Accepted Manuscript online:
December 13 2017
Citation
Gian Luca Bagnato, Natasha Irrera, Gabriele Pizzino, Domenico Santoro, William Neal Roberts, Gianfilippo Bagnato, Giovanni Pallio, Mario Vaccaro, Francesco Squadrito, Antonino Saitta, Domenica Altavilla, Alessandra Bitto; Dual αvβ3 and αvβ5 blockade attenuates fibrotic and vascular alterations in a murine model of systemic sclerosis. Clin Sci (Lond) 31 January 2018; 132 (2): 231–242. doi: https://doi.org/10.1042/CS20171426
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