title: 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.
authors: Department of Internal Medicine, Toho University School of Medicine, Sakura Hospital, Sakura City, Chiba, Japan. yasuo23@sakura.med.toho-u.ac.jp
authors: Yasuo
authors: Y
authors: Matsuzawa
authors: Tatsuo
authors: T
authors: Kawashima
authors: Risa
authors: R
authors: Yamazaki
authors: Erika
authors: E
authors: Yamaura
authors: Tomohiko
authors: T
authors: Makiyama
authors: Hiromichi
authors: H
authors: Fujino
authors: Toshihiko
authors: T
authors: Murayama
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000199:Actins / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D005333:Fetus; D005347:Fibroblasts; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008148:Lovastatin / Q000494:pharmacology*; D008168:Lung; D010713:Phosphatidylcholines / Q000494:pharmacology; D011341:Probucol / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D000975:Antioxidants; D000960:Hypolipidemic Agents; D010713:Phosphatidylcholines; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D008148:Lovastatin; D013482:Superoxide Dismutase; C434045:lecithinized superoxide dismutase; D024502:alpha-Tocopherol; D011341:Probucol; D000111:Acetylcysteine