Expression of Fibroblast Activation Protein in Mouse Pulmonary Fibrosis Model_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

WEI Li ^1# , DONG Li ¹ , JIN Zhanfeng ^1,2 , FUZhijun. ²

Department of Forensic Medicine and Pathology, Harbin Medical University.Harbin, Heilongjiang,150081, ChinaCorresponding Author: JIN Zhan-feng, E-mail: jinzf2003@ yahoo. com. cn;

Corresponding author：

Keywords：

Fibroblast activation protein; Lung fibrosis; Fibroblast; Trarisforming growth factor β1

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Objective To investigate the expression of fibroblast activation protein( FAP) in mouse pulmonary fibrosis and the relationship between FAP and trarisforming growth factor β1 ( TGF-β1 ) .Methods The mouse model with pulmonary fibrosis was established by intratracheally instillation of bleomycin. The expressions of FAP, α-smooth muscle action( α-SMA) , and TGF-β1 in lung tissues were detected with immunohistochemical technique. Results There was no expression of FAP in the normal lung tissue. In the pulmonary fibrosis mice, FAP was found in the fibroblasts existed in bronchiolar adventitia or peribronchiolar ( and perivascular) connective tissue. In the fibroblast foci, the localizations of α-SMA, TGF-β1 , and FAP were similar, but the expression of FAP was more extensive than that of α-SMA and ber than that of
TGF-β1 . The degree of lung fibrosis was bly correlated with FAP, α-SMA, and TGF-β1 ( r = 0. 795,0. 766,0. 628; P lt; 0. 01) . A significantly positive correlation was also observed between TGF-β1 and FAP( r =0. 706, P lt; 0. 01) . Conclusions FAP is especially expressed in the fibroblast foci in pulmonaryfibrosis and bly correlated with the severity of pulmonary fibrosis. FAP and TGF-β1 possibly play a synergistic role in the progression of pulmonary fibrosis.

Citation： WEI Li,DONG Li,JIN Zhanfeng,FUZhijun.. Expression of Fibroblast Activation Protein in Mouse Pulmonary Fibrosis Model. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(3): 301-305. doi: Copy

1.	Ramos C, Monta??o M, García-Alvarez J, et al. Fibroblasts fromidiopathic pulmonary fibrosis and normal lungs differ in growth rate,apoptosis, and tissue inhibitor of metalloproteinases expression. AmJRespir Cell Mol Biol, 2001, 24 : 591-598 .
2.	Flavell SJ, Hou TZ, Lax S, et al. Fibroblasts as novel therapeutictargets in chronic inflammation. Br J Pharmacol, 2008, 153: S241-S246.
3.	Wang XM, Yao TW, Nadvi NA, et al. Fibroblast activation proteinand chronic liver disease. Front Biosci, 2008, 13: 3168-3180.
4.	Szapiel SV, Elson NA, Fulmer JD, et al. Bleomycin-inducedinterstitial pulmonary disease in the nude, athymic mouse. Am RevRespir Dis, 1979, 120 : 893-899.
5.	Acharya PS, Zukas A, Chandan V, et al. Fibroblast activationprotein: a serine protease expressed at the remodeling interface in idiopathic pulmonary fibrosis. Hum Pathol, 2006, 37 : 352-360.
6.	Scotton CJ, Chambers RC. Molecular targets in pulmonary fibrosis:the myofibroblast in focus. Chest, 2007 , 132: 1311-1321.
7.	Wang XM, Yu DM, McCaughan GW, et al. Fibroblast activationprotein increases apoptosis, cell adhesion, and migration by the LX-2 human stellate cell line. Hepatology, 2005 , 42: 935-945.
8.	Artym VV, Kindzelskii AL, Chen WT, et al. Molecular proximity ofseprase and the urokinase-type plasminogen activator receptor on malignant melanoma cell membranes: dependence on beta1 integrins and the cytoskeleton. Carcinogenesis, 2002, 23: 1593-1601.
9.	Chen WT. DPPIV and seprase in cancer invasion and angiogenesis.Adv Exp Med Biol, 2003 , 524: 197-203.
10.	Huang Y, Wang S, Kelly T. Seprase promotes rapid tumor growth and increased microvessel density in a mouse model of human breast cancer. Cancer Res, 2004 , 64: 2712-2716.
11.	Aimes RT, Zijlstra A, Hooper JD, et al. Endothelial cell serine proteases expressed during vascular morphogenesis and angiogenesis. Thromb Haemost, 2003, 89: 561-572 .
12.	Noble PW, Homer RJ. Idiopathic pulmonary fibrosis: new insights into pathogenesis. Clin Chest Med, 2004, 25: 749-758 .
13.	王兴胜, 崔社怀, 杨雪梅, 等. 肺组织血管生成变化与肺纤维化关系探讨. 中国呼吸与危重监护杂志, 2007, 6 : 378-380.
14.	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.
15.	Rettig WJ, Su SL, Fortunato SR, et al. Fibroblast activation protein: purification, epitope mapping and induction by growth factors. Int JCancer, 1994 , 58: 385 -392.
16.	Willis BC, duBois RM, Borok Z. Epithelial origin of myofibroblasts during fibrosis in the lung. Proc Am Thorac Soc, 2006, 3: 377-382.
17.	蔡琳, 吴壮, 徐军. 博莱霉素诱导α平滑肌肌动蛋白Cre 重组酶转基因小鼠肺纤维化上皮细胞-间质转分化的研究. 中国呼吸与危重监护杂志, 2009, 8 , 52 -56.

1. Ramos C, Monta??o M, García-Alvarez J, et al. Fibroblasts fromidiopathic pulmonary fibrosis and normal lungs differ in growth rate,apoptosis, and tissue inhibitor of metalloproteinases expression. AmJRespir Cell Mol Biol, 2001, 24 : 591-598 .
2. Flavell SJ, Hou TZ, Lax S, et al. Fibroblasts as novel therapeutictargets in chronic inflammation. Br J Pharmacol, 2008, 153: S241-S246.
3. Wang XM, Yao TW, Nadvi NA, et al. Fibroblast activation proteinand chronic liver disease. Front Biosci, 2008, 13: 3168-3180.
4. Szapiel SV, Elson NA, Fulmer JD, et al. Bleomycin-inducedinterstitial pulmonary disease in the nude, athymic mouse. Am RevRespir Dis, 1979, 120 : 893-899.
5. Acharya PS, Zukas A, Chandan V, et al. Fibroblast activationprotein: a serine protease expressed at the remodeling interface in idiopathic pulmonary fibrosis. Hum Pathol, 2006, 37 : 352-360.
6. Scotton CJ, Chambers RC. Molecular targets in pulmonary fibrosis:the myofibroblast in focus. Chest, 2007 , 132: 1311-1321.
7. Wang XM, Yu DM, McCaughan GW, et al. Fibroblast activationprotein increases apoptosis, cell adhesion, and migration by the LX-2 human stellate cell line. Hepatology, 2005 , 42: 935-945.
8. Artym VV, Kindzelskii AL, Chen WT, et al. Molecular proximity ofseprase and the urokinase-type plasminogen activator receptor on malignant melanoma cell membranes: dependence on beta1 integrins and the cytoskeleton. Carcinogenesis, 2002, 23: 1593-1601.
9. Chen WT. DPPIV and seprase in cancer invasion and angiogenesis.Adv Exp Med Biol, 2003 , 524: 197-203.
10. Huang Y, Wang S, Kelly T. Seprase promotes rapid tumor growth and increased microvessel density in a mouse model of human breast cancer. Cancer Res, 2004 , 64: 2712-2716.
11. Aimes RT, Zijlstra A, Hooper JD, et al. Endothelial cell serine proteases expressed during vascular morphogenesis and angiogenesis. Thromb Haemost, 2003, 89: 561-572 .
12. Noble PW, Homer RJ. Idiopathic pulmonary fibrosis: new insights into pathogenesis. Clin Chest Med, 2004, 25: 749-758 .
13. 王兴胜, 崔社怀, 杨雪梅, 等. 肺组织血管生成变化与肺纤维化关系探讨. 中国呼吸与危重监护杂志, 2007, 6 : 378-380.
14. 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.
15. Rettig WJ, Su SL, Fortunato SR, et al. Fibroblast activation protein: purification, epitope mapping and induction by growth factors. Int JCancer, 1994 , 58: 385 -392.
16. Willis BC, duBois RM, Borok Z. Epithelial origin of myofibroblasts during fibrosis in the lung. Proc Am Thorac Soc, 2006, 3: 377-382.
17. 蔡琳, 吴壮, 徐军. 博莱霉素诱导α平滑肌肌动蛋白Cre 重组酶转基因小鼠肺纤维化上皮细胞-间质转分化的研究. 中国呼吸与危重监护杂志, 2009, 8 , 52 -56.

Chinese Journal of Respiratory and Critical Care Medicine

Expression of Fibroblast Activation Protein in Mouse Pulmonary Fibrosis Model

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