Dual {alpha}v{beta}3 And {alpha}v{beta}5 Blockade Attenuates Fibrotic And Vascular Alterations In A Murine Model Of Systemic Sclerosis

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 pro-fibrotic processes. SSc fibroblasts express both αvβ3 and αvβ5 integrins and their activation induces myofibroblasts differentiation. The aim of this 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-1/i.p./day) was started four 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-b1 by western blot and gene expression. Both cutaneous and pulmonary fibrosis induced by HOCl were attenutated by cilengitide treatment. Cilengitide administration reduced a-SMA, TGF-b1 e p-FAK expression and the increased deposition of fibrillar collagen in the heart and prevented glomeruli collapse in the kidneys. The inhibition of aβ3 and a&be...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research