Objective: To evaluate the influence of endothelin-1 (ET-1) and sex hormones on cell proliferation and extracellular matrix (ECM) synthesis (i.e. fibronectin, laminin) by cultured normal and scleroderma (SSc) human skin fibroblasts (FB).
Methods: Primary cultures of FB were treated with ET-1 and sex hormones (17 beta-estradiol or testosterone) for 24 hours. Cell growth was analysed by methiltetrazolium salt test, ECM synthesis was evaluated by immunocytochemistry and Western blot, both at 24 hours.
Results: In normal FB, ET-1 and 17beta-estradiol, as well as their combination, increased cell growth (p<0.001, p<0.001, p<0.01 vs untreated cells (cnt), respectively) and fibronectin synthesis (p<0.05, p<0.05, p<0.01 vs cnt, respectively). On the contrary, testosterone either alone or in combination with ET-1 did not influence cell proliferation, but decreased fibronectin synthesis (p<0.05, testosterone vs cnt). In SSc FB, ET-1 and 17beta-estradiol alone or their combination induced an increased fibronectin synthesis (p<0.05, p<0.05, p<0.01 vs cnt, respectively). Unexpectedly, testosterone induced an increase of fibronectin synthesis (p<0.05 vs cnt).
Conclusions: In conclusion, both ET-1 and 17beta-estradiol seem to exert a profibrotic effect in both normal and SSc cultured FB and might suggest their synergistic effect in the pathogenesis of the fibrotic process in SSc.