Detection of Epithelial to Mesenchymal Transition in Airways of a Bleomycin Induced Pulmonary Fibrosis Model Derived From an α-Smooth Muscle Actin-Cre Transgenic Mouse_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

CAI Lin , WU Zhuang , XU Jun

Guangzhou Medical College, Guangzhou Institute of Respiratory Disease. Guangzhou, Guangdong,510120, China;

Corresponding author：

Keywords：

Epithelial to mesenchymal transition; Pulmonary fibrosis; Bleomycin; Cre recombinase; α-smooth muscle actin; Transgenic mice

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Objective To explore whether epithelial to mesenchymal transition ( EMT) occurs in bleomycin( BLM) induced pulmonary fibrosis, and the involvement of bronchial epithelial cells( BECs) in the EMT. Methods BLM-induced peribronchial fibrosis in an α-smooth muscle actin-Cre transgenic mouse( α-SMACre /R26R) was examined by pulmonary βgal staining and α-SMA immunofluorescence staining. Results BLMtreated mice showed significantly enhanced βgal staining in subepithelial areas in bronchi, terminal bronchioles and walls of pulmonary vessels. Some alveolar epithelial cells( AECs) in certain peribronchial areas or even a small subset of BECs were also positively stained, as confirmed by α-SMA immunostaining. Conclusions EMT occurs in BLM-induced peribronchial fibrosis mice. BECs, like AECs, have the capacity to undergo EMT and to contribute to mesenchymal expansion in pulmonary fibrosis.

Citation： CAI Lin,WU Zhuang,XU Jun. Detection of Epithelial to Mesenchymal Transition in Airways of a Bleomycin Induced Pulmonary Fibrosis Model Derived From an α-Smooth Muscle Actin-Cre Transgenic Mouse. Chinese Journal of Respiratory and Critical Care Medicine, 2009, 09(1): 52-56. doi: Copy

1.	Kuhn C, McDonald JA. The roles of the myofibroblast in idiopathic pulmonary fibrosis. Ultrastructural and immunohistochemical features of sites of active extracellular matrix synthesis. Am J Pathol, 1991 ,138: 1257-1265.
2.	Schissel SL, Layne MD. Telomerase, myofibroblasts, and pulmonary fibrosis. Am J Respir Cell Mol Biol, 2006, 34: 520-522.
3.	White ES, Atrasz RG, Hu B, et al. Negative regulation of myofibroblast differentiation by PTEN ( Phosphatase and Tensin Homolog Deleted on chromosome 10. Am J Respir Crit Care Med, 2006, 173 :112 -121.
4.	Kasai H, Allen JT, Mason RM, et al. TGF-betal induces human alveolar epithelial to mesenchymal cell transition ( EMT) . Respir Res,2005, 6: 56.
5.	Hamilton DL, Abremski K. Site-specific recombination by the bacteriophage P1 lox-Cre system. Cre-mediated synapsis of two lox sites. J Mol Biol, 1984, 178: 481-486.
6.	Willis BC, Liebler JM, Luby-Phelps K, et al. Induction of epithelialmesenchymal transition in alveolar epithelial cells by transforming growth factor-betal: potential role in idiopathic pulmonary fibrosis.Am J Pathol, 2005, 166: 1321-1332.
7.	Yao HW, Xie QM, Chen JQ, et al. TGF-beta induces alveolar epithelial to mesenchymal transition in vitro. Life Sci, 2004, 76: 29-37.
8.	杨蕾蕾, 吴壮, 程萱, 等. 平滑肌细胞特异表达Cre 重组酶转基因小鼠的建立. 军事医学科学院院刊, 2005, 29: 219-222.
9.	Kim KK, Kugler MC, Wolters PJ, et al. Alveolar epithelial cellmesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci USA, 2006 ,103: 13180-13185.
10.	Metzger D, Clifford J, Chiba H, et al. Conditional site-specific recombination in mammalian cells using a liganddependent chimeric Cre recombinase. Proc Natl Acad Sci USA, 1995, 92: 6991-6995.
11.	Grinnell F, Ho CH. Transforming growth factor beta stimulates fibroblast-collagen matrix contraction by different mechanisms in mechanically loaded and unloaded matrices. Exp Cell Res, 2002, 273 :248 -255.
12.	Borzone G, Moreno R, Urrea R, et al. Bleomycin-induced chroniclung damage does not resemble human idiopathic pulmonary fibrosis.Am J Respir Crit Care Med, 2001, 163: 1648-1653.
13.	张敏, 徐军. MAPKs 通路在转化生长因子β1 诱导气道上皮细胞转化中的作用. 中国呼吸与危重监护杂志, 2007, 6: 440-443.

1. Kuhn C, McDonald JA. The roles of the myofibroblast in idiopathic pulmonary fibrosis. Ultrastructural and immunohistochemical features of sites of active extracellular matrix synthesis. Am J Pathol, 1991 ,138: 1257-1265.
2. Schissel SL, Layne MD. Telomerase, myofibroblasts, and pulmonary fibrosis. Am J Respir Cell Mol Biol, 2006, 34: 520-522.
3. White ES, Atrasz RG, Hu B, et al. Negative regulation of myofibroblast differentiation by PTEN ( Phosphatase and Tensin Homolog Deleted on chromosome 10. Am J Respir Crit Care Med, 2006, 173 :112 -121.
4. Kasai H, Allen JT, Mason RM, et al. TGF-betal induces human alveolar epithelial to mesenchymal cell transition ( EMT) . Respir Res,2005, 6: 56.
5. Hamilton DL, Abremski K. Site-specific recombination by the bacteriophage P1 lox-Cre system. Cre-mediated synapsis of two lox sites. J Mol Biol, 1984, 178: 481-486.
6. Willis BC, Liebler JM, Luby-Phelps K, et al. Induction of epithelialmesenchymal transition in alveolar epithelial cells by transforming growth factor-betal: potential role in idiopathic pulmonary fibrosis.Am J Pathol, 2005, 166: 1321-1332.
7. Yao HW, Xie QM, Chen JQ, et al. TGF-beta induces alveolar epithelial to mesenchymal transition in vitro. Life Sci, 2004, 76: 29-37.
8. 杨蕾蕾, 吴壮, 程萱, 等. 平滑肌细胞特异表达Cre 重组酶转基因小鼠的建立. 军事医学科学院院刊, 2005, 29: 219-222.
9. Kim KK, Kugler MC, Wolters PJ, et al. Alveolar epithelial cellmesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proc Natl Acad Sci USA, 2006 ,103: 13180-13185.
10. Metzger D, Clifford J, Chiba H, et al. Conditional site-specific recombination in mammalian cells using a liganddependent chimeric Cre recombinase. Proc Natl Acad Sci USA, 1995, 92: 6991-6995.
11. Grinnell F, Ho CH. Transforming growth factor beta stimulates fibroblast-collagen matrix contraction by different mechanisms in mechanically loaded and unloaded matrices. Exp Cell Res, 2002, 273 :248 -255.
12. Borzone G, Moreno R, Urrea R, et al. Bleomycin-induced chroniclung damage does not resemble human idiopathic pulmonary fibrosis.Am J Respir Crit Care Med, 2001, 163: 1648-1653.
13. 张敏, 徐军. MAPKs 通路在转化生长因子β1 诱导气道上皮细胞转化中的作用. 中国呼吸与危重监护杂志, 2007, 6: 440-443.

Chinese Journal of Respiratory and Critical Care Medicine

Detection of Epithelial to Mesenchymal Transition in Airways of a Bleomycin Induced Pulmonary Fibrosis Model Derived From an α-Smooth Muscle Actin-Cre Transgenic Mouse

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