Fluorofenidone Attenuates TGF-β1–Induced Lung Fibroblast Activation via Restoring the Expression of Caveolin-1. Issue 2 (February 2015)

• Record Type: Journal Article
• Authors: Liu, Jingjing; Song, Cheng; Xiao, Qiming; Hu, Gaoyun; Tao, Lijian; Meng, Jie
• Is Part Of: Shock. Volume 43:Issue 2(2015:Feb.)
• Publication Date: 2015-02
• Subjects: Shock -- Periodicals; Shock -- Periodicals; Choc (Pathologie) -- Périodiques; Shock; Periodicals; 616.0475
• DOI: 10.1097/SHK.0000000000000273
• Languages: English
• ISSNs: 1073-2322

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>ABSTRACT</title> <p>Caveolin-1 plays an important role in the pathogenesis of idiopathic pulmonary fibrosis. We previously showed that fluorofenidone (FD), a novel pyridine agent, can attenuate bleomycin-induced experimental pulmonary fibrosis and restore the production of caveolin-1. In this study, we explore mainly whether caveolin-1 plays a critical role in the anti–pulmonary fibrosis effects of FD <italic>in vitro</italic>. The normal human lung fibroblasts (NHLFs) were cultured with transforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>) and then were treated with FD. Subsequently, NHLFs transfected with cav-1-siRNA were treated with TGF-β<sub>1</sub> and/or FD. The expressions of α-smooth muscle actin (α-SMA), fibronectin, collagen I, caveolin-1, phosphorylated extracellular signal–regulated kinase (p-ERK), phosphorylated <italic>c</italic>-Jun <italic>N</italic>-terminal kinase (p-JNK), and phosphorylated P38 were measured by Western blot and/or real-time polymerase chain reaction. Fluorofenidone attenuated TGF-β<sub>1</sub>–induced expressions of α-SMA, fibronectin, and collagen I; inhibited phosphorylation of ERK, JNK, and P38; and restored caveolin-1 protein expression but cannot increase caveolin-1 mRNA level <italic>in vitro</italic>. After caveolin-1 was silenced, FD could not downregulate TGF-β<sub>1</sub>–induced expressions of α-SMA, fibronectin, and collagen I or phosphorylation of ERK, JNK, and P38. These studies demonstrate that FD, a potential antifibrotic agent, may attenuate TGF-β<sub>1</sub>–induced activation of NHLFs by restoring the expression of caveolin-1.</p> </sec> </abstract>