Effects of bosentan on collagen type I synthesis on in vitro culture of scleroderma skin fibroblasts

Abstract

The present study evaluated the effects of a non-selective endothelin (ET_A/B) receptors antagonist, on collagen type I (COLI) synthesis on in vitro culture of scleroderma (SSc) skin fibroblasts (Fb). Fb were obtained from skin biopsies of 6 female SSc patients (mean age 64. 1±6 years), after informed consent and Ethical Committee Approval. Cells were treated with endothelin-I [ET-I, 100nM] for 24 and 48 hrs, pre-treated for I hr with ET_A/B receptors antagonist [10nM] alone or followed by ET-I for 24 and 48 hrs. Untreated Fb were used as controls. Immunocytochemistry and western blot analysis were performed to evaluate COLI synthesis. ET-I increased COLI synthesis both at 24 and 48 hrs when compared to controls. ET_A/B receptor antagonost blocks the increased COLI synthesis ET-I-mediated both at 24 and 48 hrs vs. ET-I. Results showed that ET-I receptors blockage by ET_A/B receptors antagonist might prevent the excessive synthesis of COLI, supporting its positive action in the management of skin fibrosis.

Keywords

• endothelin-1
• ETa/ETb receptor antagonist
• fibrosis
• systemic sclerosis