Fluorofenidone attenuates TGF-β1-induced lung fibroblast activation via restoring the expression of caveolin-1.

Abstract

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.

• Authors: Jingjing Liu, Cheng Song, Qiming Xiao, Gaoyun Hu, Lijian Tao, Jie Meng
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 43 Issue 2 Pg. 201-7 (Feb 2015) ISSN: 1540-0514 [Electronic] United States
• PMID: 25394239 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5-methyl-1-(3-fluorophenyl)-2-(1H)-pyridone
• ACTA2 protein, human
• Actins
• Caveolin 1
• Collagen Type I
• Fibronectins
• Pyridones
• RNA, Messenger
• Transforming Growth Factor beta1
• Extracellular Signal-Regulated MAP Kinases
• p38 Mitogen-Activated Protein Kinases
• MAP Kinase Kinase 4

Topics

• Actins (biosynthesis, genetics)
• Caveolin 1 (biosynthesis, genetics)
• Cells, Cultured
• Collagen Type I (biosynthesis, genetics)
• Dose-Response Relationship, Drug
• Enzyme Activation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Fibroblasts (drug effects, metabolism)
• Fibronectins (biosynthesis, genetics)
• Gene Expression Regulation (drug effects)
• Gene Silencing
• Humans
• Idiopathic Pulmonary Fibrosis (metabolism, pathology)
• Lung (metabolism, pathology)
• MAP Kinase Kinase 4 (metabolism)
• Pyridones (administration & dosage, pharmacology)
• RNA, Messenger (genetics)
• Transforming Growth Factor beta1 (antagonists & inhibitors, pharmacology)
• p38 Mitogen-Activated Protein Kinases (metabolism)