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Addolorata Corrado
Ruolo
Ricercatore
Organizzazione
Università degli Studi di Foggia
Dipartimento
Dipartimento di Scienze Mediche e Chirurgiche
Area Scientifica
Area 06 - Scienze mediche
Settore Scientifico Disciplinare
MED/16 - Reumatologia
Settore ERC 1° livello
LS - Life sciences
Settore ERC 2° livello
LS4 Physiology, Pathophysiology and Endocrinology: Organ physiology, pathophysiology, endocrinology, metabolism, ageing, tumorigenesis, cardiovascular disease, metabolic syndrome
Settore ERC 3° livello
LS4_1 Organ physiology and pathophysiology
AIM: The aim of the study was to investigate the effect of selective ETRA Sitaxsentan on viability and differentiation into myofibroblasts of lung fibroblasts derived from SSc-ILD patients and the ability of this drug to modify the lung fibroblast synthesis of VEGF, type I collagen and fibronectin. METHODS: Primary human lung fibroblast cultures were obtained from BAL of SSc-ILD patients. Cell cultures were exposed for 48 h to crescent concentrations of Sitaxsentan (10 -6M to 10 -4M). In these experimental conditions we evaluated cell viability through crystal violet staining, the production and mRNA expression of VEGF, fibronectin and type I collagen respectively through ELISA and real-Time PCR. Further, we detected alpha-Smooth Muscle Actin (α-SMA) through immunocytochemical assay. RESULTS: The lowest concentration of sitaxsentan (10-6M) did not affect fibroblasts viability; conversely at higher concentrations, sitaxsentan induced a significant inhibition of cell viability. Synthesis and mRNA expression of VEGF, type 1 collagen and fibronectin were significantly reduced in treated lung fibroblasts compared to the untreated ones, in a dose-dependent manner. At higher concentrations, Sitaxsentan reduced the expression of α-SMA. CONCLUSION: The results of this study show that sitaxentan is able in vitro to reduce both cell viability than production of VEGF and extra-cellular matrix components in SSc lung fibroblasts, confirming the anti-fibrotic potential of ETRA in SSc. The decreased expression of α-SMA in treated cells indicate that sitaxsentan may inhibit the fibroblast differentiation toward a myo-fibroblast phenotype and further support the hypothesis that the selective ETRAs may be beneficial in patients with SSc-ILD as anti fibrotic agents.
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