• Jingjing Liu, Cheng Song, Qiming Xiao, Gaoyun Hu, Lijian Tao, and Jie Meng.
• *Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha; †Department of Respiratory Medicine, Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science and Technology, Wuhan; ‡Pharmaceutical School, Central South University; and §Department of Nephrology Medicine, Xiangya Hospital, Central South University, Changsha; and ∥State Key Lab of Respiratory Disease and National Clinical Research Center for Respiratory Disease, Guangzhou, China.
• Shock. 2015 Feb 1;43(2):201-7.

AbstractCaveolin-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 in vitro. The normal human lung fibroblasts (NHLFs) were cultured with transforming growth factor-β1 (TGF-β1) and then were treated with FD. Subsequently, NHLFs transfected with cav-1-siRNA were treated with TGF-β1 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 c-Jun N-terminal kinase (p-JNK), and phosphorylated P38 were measured by Western blot and/or real-time polymerase chain reaction. Fluorofenidone attenuated TGF-β1-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 in vitro. After caveolin-1 was silenced, FD could not downregulate TGF-β1-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-β1-induced activation of NHLFs by restoring the expression of caveolin-1.

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