Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by the development of subpleural foci of myofibroblasts that contribute to the exuberant fibrosis. Recent studies revealed that pleural mesothelial cells (PMCs) undergo epithelial-mesenchymal transition (EMT) and play a pivotal role in IPF. In animal model, bleomycin induces pulmonary fibrosis exhibiting subpleural fibrosis similar to what is seen in human IPF. It is not known yet whether bleomycin induces EMT in PMCs. In the present study, PMCs were cultured and treated with bleomycin. The protein levels of collagen-I, mesenchymal phenotypic markers (vimentin and α-smooth muscle actin), and epithelial phenotypic markers (cytokeratin-8 and E-cadherin) were measured by Western blot. PMC migration was evaluated using wound-healing assay of culture PMCs in vitro, and in vivo by monitoring the localization of PMC marker, calretinin, in the lung sections of bleomycin-induced lung fibrosis. The results showed that bleomycin induced increases in collagen-I synthesis in PMC. Bleomycin induced significant increases in mesenchymal phenotypic markers and decreases in epithelial phenotypic markers in PMC, and promoted PMC migration in vitro and in vivo. Moreover, TGF-β1-Smad2/3 signaling pathway involved in the EMT of PMC was demonstrated. Taken together, our results indicate that bleomycin induces characteristic changes of EMT in PMC and the latter contributes to subpleural fibrosis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 75-82 |
| Number of pages | 8 |
| Journal | Toxicology and Applied Pharmacology |
| Volume | 283 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 1 2015 |
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Keywords
- Bleomycin
- Collagen
- Epithelial-mesenchymal transition (EMT)
- Fibrosis
- Lung
- Pleural mesothelial cell
ASJC Scopus subject areas
- Toxicology
- Pharmacology
Cite this
Bleomycin induced epithelial-mesenchymal transition (EMT) in pleural mesothelial cells. / Chen, Li Jun; Ye, Hong; Zhang, Qian; Li, Feng Zhi; Song, Lin Jie; Yang, Jie; Mu, Qing; Rao, Shan Shan; Cai, Peng Cheng; Xiang, Fei; Zhang, Jian Chu; Su, Yunchao; Xin, Jian Bao; Ma, Wan Li.
In: Toxicology and Applied Pharmacology, Vol. 283, No. 2, 01.03.2015, p. 75-82.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Bleomycin induced epithelial-mesenchymal transition (EMT) in pleural mesothelial cells
AU - Chen, Li Jun
AU - Ye, Hong
AU - Zhang, Qian
AU - Li, Feng Zhi
AU - Song, Lin Jie
AU - Yang, Jie
AU - Mu, Qing
AU - Rao, Shan Shan
AU - Cai, Peng Cheng
AU - Xiang, Fei
AU - Zhang, Jian Chu
AU - Su, Yunchao
AU - Xin, Jian Bao
AU - Ma, Wan Li
PY - 2015/3/1
Y1 - 2015/3/1
N2 - Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by the development of subpleural foci of myofibroblasts that contribute to the exuberant fibrosis. Recent studies revealed that pleural mesothelial cells (PMCs) undergo epithelial-mesenchymal transition (EMT) and play a pivotal role in IPF. In animal model, bleomycin induces pulmonary fibrosis exhibiting subpleural fibrosis similar to what is seen in human IPF. It is not known yet whether bleomycin induces EMT in PMCs. In the present study, PMCs were cultured and treated with bleomycin. The protein levels of collagen-I, mesenchymal phenotypic markers (vimentin and α-smooth muscle actin), and epithelial phenotypic markers (cytokeratin-8 and E-cadherin) were measured by Western blot. PMC migration was evaluated using wound-healing assay of culture PMCs in vitro, and in vivo by monitoring the localization of PMC marker, calretinin, in the lung sections of bleomycin-induced lung fibrosis. The results showed that bleomycin induced increases in collagen-I synthesis in PMC. Bleomycin induced significant increases in mesenchymal phenotypic markers and decreases in epithelial phenotypic markers in PMC, and promoted PMC migration in vitro and in vivo. Moreover, TGF-β1-Smad2/3 signaling pathway involved in the EMT of PMC was demonstrated. Taken together, our results indicate that bleomycin induces characteristic changes of EMT in PMC and the latter contributes to subpleural fibrosis.
AB - Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by the development of subpleural foci of myofibroblasts that contribute to the exuberant fibrosis. Recent studies revealed that pleural mesothelial cells (PMCs) undergo epithelial-mesenchymal transition (EMT) and play a pivotal role in IPF. In animal model, bleomycin induces pulmonary fibrosis exhibiting subpleural fibrosis similar to what is seen in human IPF. It is not known yet whether bleomycin induces EMT in PMCs. In the present study, PMCs were cultured and treated with bleomycin. The protein levels of collagen-I, mesenchymal phenotypic markers (vimentin and α-smooth muscle actin), and epithelial phenotypic markers (cytokeratin-8 and E-cadherin) were measured by Western blot. PMC migration was evaluated using wound-healing assay of culture PMCs in vitro, and in vivo by monitoring the localization of PMC marker, calretinin, in the lung sections of bleomycin-induced lung fibrosis. The results showed that bleomycin induced increases in collagen-I synthesis in PMC. Bleomycin induced significant increases in mesenchymal phenotypic markers and decreases in epithelial phenotypic markers in PMC, and promoted PMC migration in vitro and in vivo. Moreover, TGF-β1-Smad2/3 signaling pathway involved in the EMT of PMC was demonstrated. Taken together, our results indicate that bleomycin induces characteristic changes of EMT in PMC and the latter contributes to subpleural fibrosis.
KW - Bleomycin
KW - Collagen
KW - Epithelial-mesenchymal transition (EMT)
KW - Fibrosis
KW - Lung
KW - Pleural mesothelial cell
UR - http://www.scopus.com/inward/record.url?scp=84921850946&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84921850946&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2015.01.004
DO - 10.1016/j.taap.2015.01.004
M3 - Article
C2 - 25595642
AN - SCOPUS:84921850946
VL - 283
SP - 75
EP - 82
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 2
ER -