Fluorofenidone attenuates TGF-β1-induced lung fibroblast activation via restoring the expression of caveolin-1.
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 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.
*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.
Jingjing
J
Liu
Cheng
C
Song
Qiming
Q
Xiao
Gaoyun
G
Hu
Lijian
L
Tao
Jie
J
Meng
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D051242:Caveolin 1 / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C511655:5-methyl-1-(3-fluorophenyl)-2-(1H)-pyridone; C541116:ACTA2 protein, human; D000199:Actins; D051242:Caveolin 1; D024042:Collagen Type I; D005353:Fibronectins; D011728:Pyridones; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4