Inhibition of Plasminogen Activator Inhibitor-1 Expression in Smoke-Exposed Alveolar Type II Epithelial Cells Attenuates Epithelial-Mesenchymal Transition.
10.4046/trd.2011.70.6.462
- Author:
Jeong Sup SONG
1
;
Chun Mi KANG
Author Information
1. Department of Internal Medicine, Yeouido St Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea. jssong@catholic.ac.kr
- Publication Type:Original Article
- Keywords:
Plasminogen Activator Inhibitor 1;
Epithelial-Mesenchymal Transition;
Pulmonary Fibrosis
- MeSH:
Animals;
Blotting, Western;
Epithelial Cells;
Epithelial-Mesenchymal Transition;
Idiopathic Pulmonary Fibrosis;
Indoleacetic Acids;
Lung;
Phosphorylation;
Plasminogen;
Plasminogen Activator Inhibitor 1;
Plasminogen Activators;
Polymerase Chain Reaction;
Povidone;
Pulmonary Fibrosis;
Rats;
Risk Factors;
RNA, Small Interfering;
Silicon Dioxide;
Smoke;
Smoking;
Snails;
Transfection
- From:Tuberculosis and Respiratory Diseases
2011;70(6):462-473
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Smoking is a risk factor for idiopathic pulmonary fibrosis (IPF), but the mechanism of the association remains obscure. There is evidence demonstrating that plasminogen activator inhibitor-1 (PAI-1) is involved in the progression of pulmonary fibrosis. This study was to determine whether the administration of small interfering RNA (siRNA) targeting PAI-1 or PAI-1 inhibitor to the cigarette smoking extract (CSE)-exposed rat alveolar type II epithelial cells (ATII cells) limits the epithelial-mesenchymal transition (EMT). METHODS: ATII cells were isolated from lung of SD-rat using percoll gradient method and cultured with 5% CSE. The EMT was determined from the ATII cells by measuring the real-time RT PCR and western blotting after the PAI-1 siRNA transfection to the cells and after administration of tiplaxtinin, an inhibitor of PAI-1. The effect of PAI-1 inhibitor was also evaluated in the bleomycin-induced rats. RESULTS: PAI-1 was overexpressed in the smoking exposed ATII cells and was directly associated with EMT. The EMT from the ATII cells was suppressed by PAI-1 siRNA transfection or administration of tiplaxtinin. Signaling pathways for EMT by smoking extract were through the phosphorylation of SMAD2 and ERK1/2, and finally Snail expression. Tiplaxtinin also suppressed the pulmonary fibrosis and PAI-1 expression in the bleomycin-induced rats. CONCLUSION: Our data shows that CSE induces rat ATII cells to undergo EMT by PAI-1 via SMAD2-ERK1/2-Snail activation. This suppression of EMT by PAI-1 siRNA transfection or PAI-1 inhibitor in primary type II alveolar epithelial cells might be involved in the attenuation of bleomycin-induced pulmonary fibrosis in rats.
