Inhibitory effects of clinical reagents having anti-oxidative activity on transforming growth factor-β1-induced expression of α-smooth muscle actin in human fetal lung fibroblasts

Abstract

Excessive production of transforming growth factor-β1 (TGFβ1) plays an important role in lung fibrosis, in which the differentiation of fibroblasts into myofibroblasts is a key process. Increased formation of reactive oxygen species (ROS) induced by TGFβ1 is a common pathological feature of fibrosis. In the present study, probucol and lovastatin, which are therapeutics used for hyperlipidemia and proposed to act as anti-oxidants, were examined in terms of their effect on TGFβ1-induced formation of ROS and expression of α-smooth muscle actin (αSMA), a myofibroblast marker, in human fetal lung fibroblasts (HFL1 cells). The effects of anti-oxidative enzymes and reagents including N-acetyl-L-cysteine, α-tocopherol, and lecithinized-superoxide dismutase (SOD) on TGFβ1-induced expression of αSMA were also examined. Treatment with probucol (30 μM) and lovastatin (1 μM and 3 μM), in addition to lecithinized- SOD, significantly inhibited the TGFβ1-induced formation of ROS and αSMA. Other anti-oxidants including N-acetyl-L-cysteine had marginal effects on αSMA expression under the conditions. Probucol and lovastatin, established therapeutics, may be worth trying in patients with both lung fibrosis and hypercholesterolemia.