The effect of secreted frizzled-related protein 1 on airway remodeling in chronic obstructive pulmonary disease_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

YAN Xiaoyi ¹ , JIA Man ¹ , JIANG Jie ¹ , MENG Yaqi ¹ , XU Jiayan ¹ , QIAO Yingying ² ,  YAO Xin ¹

1. Department of Respiratory Medicine, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P. R. China;
2. Department of Respiratory Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P. R. China;

Corresponding?author：

YAO Xin, Email: yaoxin@njmu.edu.cn

Keywords：

Chronic obstructive pulmonary disease; Secreted frizzled-related protein 1; Human bronchial epithelial cells

DOI：

10.7507/1671-6205.201702038

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Objective To study the effect of secreted frizzled-related protein 1 (SFRP1) on airway remodeling in chronic obstructive pulmonary disease (COPD). Methods Forty-five patients with stable COPD and 21 healthy controls were collected in Jiangsu Province Hospital from June 2014 to June 2016. The level of SFRP1 in serum was detected by ELISA. The expression of SFRP1, E-cadherin and α-smooth muscle actin (α-SMA) in human bronchial epithelial cells (16HBEs) were detected by Western blot. Results The level of SFRP1 in serum of the COPD patients was significantly higher than that in the healthy controls [(80.65 ± 15.01) pg/ml vs. (23.89 ± 2.59) pg/ml, P<0.05]. There were negative correlations between serum SFRP1 levels and lung function parameters (FEV ₁, FEV ₁%pred, and FVC) in the COPD patients (correlation coefficient r value were –0.368 9, –0.382 6 and –0.417 3, respectively, all P<0.05). The level of serum SFRP1 in the COPD smokers was significantly higher than that in the COPD non-smokers [(97.74 ± 21.95) pg/mlvs. (52.51 ± 14.87) pg/ml, P<0.05]. The expression of SFRP1 could be up-regulated by cigarette smoke extract in 16HBEs. The expression of E-cadherin of 16HBEs was up-regulated by recombinant SFRP1, but the expression of α-SMA of 16HBEs was down-regulated by recombinant SFRP1. Conclusion SFRP1 may be involved in the pathogenesis of airway remodeling of COPD by regulating the expression of E-cadherin and α-SMA of bronchial epithelial cells.

Citation： YAN Xiaoyi, JIA Man, JIANG Jie, MENG Yaqi, XU Jiayan, QIAO Yingying, YAO Xin. The effect of secreted frizzled-related protein 1 on airway remodeling in chronic obstructive pulmonary disease. Chinese Journal of Respiratory and Critical Care Medicine, 2017, 16(5): 427-431. doi: 10.7507/1671-6205.201702038 Copy

1.	柳濤, 蔡柏薔. 慢性阻塞性肺疾病診斷、處理和預防全球策略(2011 年修訂版)介紹. 中國呼吸與危重監護雜志, 2012, 11(1):1-12.0.
2.	Vestbo J., Hurd SS., Agusti AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med, 2013, 187(4): 347-365.
3.	Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. Respirology, 2017, 22(3): 128-149.
4.	龐才雙, 曾妮, 申永春, 等. 慢性阻塞性肺疾病氣道重塑機制及其研究進展. 西部醫學, 2017, 29(1):135-140.0.
5.	Ota C, Baarsma HA, Wagner DE, et al. Linking bronchopulmonary dysplasia to adult chronic lung diseases: role of WNT signaling. Mol Cell Pediatr, 2016, 3(1):34.
6.	Caprioli A, Villasenor A, Wylie L A, et al. Wnt4 is essential to normal mammalian lung development. Dev Biol, 2015, 406(2): 222-234.
7.	Lehmann M, Baarsma HA, Konigshoff M. WNT signaling in lung aging and disease. Ann Am Thorac Soc, 2016, 13(Suppl 5): S411-S416.
8.	Kawano Y, Kypta R. Secreted antagonists of the Wnt signalling pathway. J Cell Sci, 2003, 116(Pt 13): 2627-2634.
9.	van Amerongen R, Berns A. Knockout mouse models to study Wnt signal transduction. Trends Genet, 2006, 22(12): 678-689.
10.	Uhl FE, Vierkotten S, Wagner DE, et al. Preclinical validation and imaging of Wnt-induced repair in human 3D lung tissue cultures. Eur Respir J, 2015, 46(4):1150-1166.
11.	Foronjy R, Imai K, Shiomi T, et al. The divergent roles of secreted frizzled related protein-1 (SFRP1) in lung morphogenesis and emphysema. Am J Pathol, 2010, 177(2): 598-607.
12.	丁寧, 王勝. 慢性阻塞性肺疾病發病機制最新研究進展. 臨床肺科雜志, 2016, 21(1):133-136.0.
13.	Kneidinger N, Yildirim AO, Callegari J, et al. Activation of the WNT/beta-catenin pathway attenuates experimental emphysema. Am J Respir Crit Care Med, 2011, 183(6): 723-733.
14.	Heijink IH, de Bruin HG, van den Berge M, et al. Role of aberrant WNT signalling in the airway epithelial response to cigarette smoke in chronic obstructive pulmonary disease. Thorax, 2013, 68(8):709-716.
15.	Wang R, Ahmed J, Wang G, et al. Down-regulation of the canonical Wnt beta-catenin pathway in the airway epithelium of healthy smokers and smokers with COPD. PLoS One, 2011, 6(4):e14793.
16.	Ren J, Wang R, Huang G, et al. sFRP1 inhibits epithelial-mesenchymal transition in A549 human lung adenocarcinoma cell line. Cancer Biother Radiopharm, 2013, 28(7): 565-571.
17.	景霞, 許建英. 吸煙對大鼠氣道上皮細胞基質金屬蛋白酶 9 表達的影響. 中國呼吸與危重監護雜志, 2009, 8(3):220-223.0.
18.	Wang A, Zsengeller ZK, Hecht JL, et al. Excess placental secreted frizzled-related protein 1 in maternal smokers impairs fetal growth. J Clin Invest, 2015, 125(11):4021-4025.
19.	Bartis D, Mise N, Mahida RY, et al. Epithelial-mesenchymal transition in lung development and disease: does it exist and is it important? Thorax, 2014, 69(8):760-765.
20.	Nowrin K, Sohal SS, Peterson G, et al. Epithelial-mesenchymal transition as a fundamental underlying pathogenic process in COPD airways: fibrosis, remodeling and cancer. Expert Rev Respir Med, 2014, 8(5):547-559.
21.	Pain M, Bermudez O, Lacoste P, et al. Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype. Eur Respir Rev, 2014, 23(131): 118-130.

1. 柳濤, 蔡柏薔. 慢性阻塞性肺疾病診斷、處理和預防全球策略(2011 年修訂版)介紹. 中國呼吸與危重監護雜志, 2012, 11(1):1-12.0.
2. Vestbo J., Hurd SS., Agusti AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med, 2013, 187(4): 347-365.
3. Vogelmeier CF, Criner GJ, Martinez FJ, et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report. Respirology, 2017, 22(3): 128-149.
4. 龐才雙, 曾妮, 申永春, 等. 慢性阻塞性肺疾病氣道重塑機制及其研究進展. 西部醫學, 2017, 29(1):135-140.0.
5. Ota C, Baarsma HA, Wagner DE, et al. Linking bronchopulmonary dysplasia to adult chronic lung diseases: role of WNT signaling. Mol Cell Pediatr, 2016, 3(1):34.
6. Caprioli A, Villasenor A, Wylie L A, et al. Wnt4 is essential to normal mammalian lung development. Dev Biol, 2015, 406(2): 222-234.
7. Lehmann M, Baarsma HA, Konigshoff M. WNT signaling in lung aging and disease. Ann Am Thorac Soc, 2016, 13(Suppl 5): S411-S416.
8. Kawano Y, Kypta R. Secreted antagonists of the Wnt signalling pathway. J Cell Sci, 2003, 116(Pt 13): 2627-2634.
9. van Amerongen R, Berns A. Knockout mouse models to study Wnt signal transduction. Trends Genet, 2006, 22(12): 678-689.
10. Uhl FE, Vierkotten S, Wagner DE, et al. Preclinical validation and imaging of Wnt-induced repair in human 3D lung tissue cultures. Eur Respir J, 2015, 46(4):1150-1166.
11. Foronjy R, Imai K, Shiomi T, et al. The divergent roles of secreted frizzled related protein-1 (SFRP1) in lung morphogenesis and emphysema. Am J Pathol, 2010, 177(2): 598-607.
12. 丁寧, 王勝. 慢性阻塞性肺疾病發病機制最新研究進展. 臨床肺科雜志, 2016, 21(1):133-136.0.
13. Kneidinger N, Yildirim AO, Callegari J, et al. Activation of the WNT/beta-catenin pathway attenuates experimental emphysema. Am J Respir Crit Care Med, 2011, 183(6): 723-733.
14. Heijink IH, de Bruin HG, van den Berge M, et al. Role of aberrant WNT signalling in the airway epithelial response to cigarette smoke in chronic obstructive pulmonary disease. Thorax, 2013, 68(8):709-716.
15. Wang R, Ahmed J, Wang G, et al. Down-regulation of the canonical Wnt beta-catenin pathway in the airway epithelium of healthy smokers and smokers with COPD. PLoS One, 2011, 6(4):e14793.
16. Ren J, Wang R, Huang G, et al. sFRP1 inhibits epithelial-mesenchymal transition in A549 human lung adenocarcinoma cell line. Cancer Biother Radiopharm, 2013, 28(7): 565-571.
17. 景霞, 許建英. 吸煙對大鼠氣道上皮細胞基質金屬蛋白酶 9 表達的影響. 中國呼吸與危重監護雜志, 2009, 8(3):220-223.0.
18. Wang A, Zsengeller ZK, Hecht JL, et al. Excess placental secreted frizzled-related protein 1 in maternal smokers impairs fetal growth. J Clin Invest, 2015, 125(11):4021-4025.
19. Bartis D, Mise N, Mahida RY, et al. Epithelial-mesenchymal transition in lung development and disease: does it exist and is it important? Thorax, 2014, 69(8):760-765.
20. Nowrin K, Sohal SS, Peterson G, et al. Epithelial-mesenchymal transition as a fundamental underlying pathogenic process in COPD airways: fibrosis, remodeling and cancer. Expert Rev Respir Med, 2014, 8(5):547-559.
21. Pain M, Bermudez O, Lacoste P, et al. Tissue remodelling in chronic bronchial diseases: from the epithelial to mesenchymal phenotype. Eur Respir Rev, 2014, 23(131): 118-130.

Chinese Journal of Respiratory and Critical Care Medicine

The effect of secreted frizzled-related protein 1 on airway remodeling in chronic obstructive pulmonary disease

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