융합정보논문지 (Journal of Convergence for Information Technology)

중소기업융합학회 (Convergence Society for SMB)
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만성폐쇄성폐질환에서 상피중간엽이행 조절을 통한 Celecoxib의 폐 손상 개선효과

Effect of Celecoxib on Lung Injury Improvement by Controlling Epithelial-Mesenchymal Transition(EMT) in Chronic Obstructive Pulmonary Disease(COPD)

  • 이선경 (동강대학교 임상병리학과)
  • Lee, Sun-Kyung (Dept. of Biomedical Laboratory Science, Donggang University)
  • 투고 : 2021.09.30
  • 심사 : 2021.11.20
  • 발행 : 2021.11.28
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초록

본 연구는 만성폐쇄성폐질환(COPD)의 동물 모델을 이용하여 Celecoxib의 폐 손상 개선효과를 연구하였다. COPD는 LPS와 담배연기추출물(CSE)로 유도하여 in vitro와 in vivo에서 병행 연구하였다. In vitro는 인간 섬유아세포(MRC5)에서 MTT assay, real-time PCR를 하였고 in vivo는 mRNA 발현, 기관지폐포세척액(BALF), collagen content, 단백질 발현을 확인하였다. 실험을 통해 Celecoxib는 BALF에서 염증세포 수의 감소와 사이토카인, soluble protein의 축적을 감소시켰고 동물모델에서는 체중과 폐 무게를 감소시켰으며, 폐 콜라젠 축적도 개선하였다. 또 웨스턴 블로팅과 real-time PCR을 통해 EMT 표지자의 감소를 확인하였다. 결과적으로 Celecoxib는 EMT를 조절하여 LPS+CSE로 유도된 COPD의 폐 손상에서 개선제로 작용할 수 있을 것으로 사료된다.

This study confirmed the effects of improving lung damage of celecoxib using an animal model of chronic obstructive pulmonary disease(COPD). It was induced in models LPS + CSE and performed in vitro and in vivo. MTT assay and real-time PCR were performed in MRC5 cells as in vitro, and mRNA expression, BALF, collagen content, and protein expression were confirmed as in vivo. Celecoxib reduced the number of inflammatory cells, cytokine and soluble protein accumulation in BALF, decreased body weight and lung weight in animal models, and improved lung collagen deposition. In addition, the reduction of EMT markers was confirmed through Western blotting and real-time PCR. Consequently, celecoxib is thought to improve lung damage of COPD induced to LPS+CSE by regulating EMT.

키워드

참고문헌

  1. M. Xie, X Liu, X Cao, M Guo & X Li. (2020). Trends in prevalence and incidence of chronic respiratory diseases from 1990 to 2017. Respir Res, 21(1), 49. https://doi.org/10.1186/s12931-020-1291-8
  2. I. Tsiligianni, E. Metting, T. van der Molen, N. Chavannes & J. Kocks. (2016). Morning and night symptoms in primary care COPD patients: a cross-sectional and longitudinal study. An UNLOCK study from the IPCRG. NPJ Prim Care Respir Med, 26. 16040. https://doi.org/10.1038/npjpcrm.2016.40
  3. J. Milara, T. Peiro, A. Serrano & J. Cortijo. (2013). Epithelial to mesenchymal transition is increased in patients with COPD and induced by cigarette smoke. Thorax, 68, 410-420. https://doi.org/10.1136/thoraxjnl-2012-201761
  4. R. Chatterjee & J. Chatterjee. (2020). ROS and oncogenesis with special reference to EMT and stemness. Eur J Cell Biol, 99, 151073. https://doi.org/10.1016/j.ejcb.2020.151073
  5. J. X. Jiang et al. (2017). Rac1 signaling regulates cigarette smoke-induced inflammation in the lung via the Erk1/2 MAPK and STAT3 pathways. Biochim Biophys Acta, 1863(7), 1778-1788. DOI : 10.1016/j.bbadis.2017.04.013
  6. D. G. Menter, R. L. Schilsky & R. N. DuBois. (2010). Cyclooxygenase-2 and cancer treatment: understanding the risk should be worth the reward. Clin. Cancer Res, 16, 1384-1390. https://doi.org/10.1158/1078-0432.CCR-09-0788
  7. T. H. Chu. (2014). Celecoxib suppresses hepatoma stemness and progression by up-regulating PTEN. Oncotarget, 5, 1475-1490. https://doi.org/10.18632/oncotarget.1745
  8. P Venkatesan. (2011). The potential of celecoxib-loaded hydroxyapatite-chitosan nanocomposite for the treatment of colon cancer. Biomaterials, 32, 3794-3806. https://doi.org/10.1016/j.biomaterials.2011.01.027
  9. D. Chakroborty. (2011). Dopamine stabilizes tumor blood vessels by up-regulating angiopoietin 1 expression in pericytes and Kruppel-like factor-2 expression in tumor endothelial cells. Proc. Natl. Acad. Sci. USA, 108, 20730-20735. https://doi.org/10.1073/pnas.1108696108
  10. K. H. Yoo, Y. S. Kim & S. S. Sheen. (2011). Prevalence of chronic obstructive pulmonary disease in Korea: the fourth Korean National Health and Nutrition Examination Survey, 2008. Respirology, 16(4), 659-665. https://doi.org/10.1111/j.1440-1843.2011.01951.x
  11. J. C. Hogg, F Chu & S Utokaparch. (2004). The nature of small-airway obstruction in chronic obstructive pulmonary disease. New England Journal of Medicine, 350(26), 2645-2653. https://doi.org/10.1056/NEJMoa032158
  12. A. Butler, G. M. Walton & E. Sapey. (2018). Neutrophilic inflammation in the pathogenesis of chronic obstructive pulmonary disease. COPD: Journal of Chronic Obstructive Pulmonary Disease, 15(4), 392-404. https://doi.org/10.1080/15412555.2018.1476475
  13. P. J. Barnes. (2009). The cytokine network in chronic obstructive pulmonary disease. American Journal of Respiratory Cell and Molecular Biology, 41(6), 631-638. https://doi.org/10.1165/rcmb.2009-0220TR
  14. M. Rincon & C. G. Irvin. (2012). Role of IL-6 in asthma and other inflammatory pulmonary diseases. International Journal of Biological Sciences, 8(9), 1281-1290. https://doi.org/10.7150/ijbs.4874
  15. V. M. Keatings, P. D. Collins, D. M. Scott & P. J. Barnes. (1996). Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. American Journal of Respiratory and Critical Care Medicine, 153(2), 530-534. https://doi.org/10.1164/ajrccm.153.2.8564092
  16. P. J. Barnes. (2008). Immunology of asthma and chronic obstructive pulmonary disease. Nature Reviews Immunology, 8(3), 183-192. https://doi.org/10.1038/nri2254
  17. G. G. Brusselle, G. F. Joos & K. R. Bracke. (2011). New insights into the immunology of chronic obstructive pulmonary disease. The Lancet, 378(9795), 1015-1026. https://doi.org/10.1016/S0140-6736(11)60988-4
  18. J. C. Hogg & W. Timens. (2009). The pathology of chronic obstructive pulmonary disease. Annual Review of Pathology: Mechanisms of Disease, 4(1), 435-459. https://doi.org/10.1146/annurev.pathol.4.110807.092145
  19. A. Soltani, S. Sohal. S. Weston, R. Wood-Baker & E. H. Walters. (2012). Vessel-associated transforming growth factor-beta1 (TGF-β1) is increased in the bronchial reticular basement membrane in COPD and normal smokers. PLoS ONE, 7(6), e39736. https://doi.org/10.1371/journal.pone.0039736
  20. M. Rincon & C. G. Irvin. (2012). Role of IL-6 in asthma and other inflammatory pulmonary diseases. International Journal of Biological Sciences, 8(9), 1281-1290. https://doi.org/10.7150/ijbs.4874
  21. M. Javier, N. Rafael, J. Gustavo, P. Teresa, S. Adela & R. Mercedes. (2012). Sphingosine-1-phosphate is increased in patients with idiopathic pulmonary fibrosis and mediates epithelial to mesenchymal transition. Thorax, 67(2), 147-156. https://doi.org/10.1136/thoraxjnl-2011-200026
  22. N. Kaosia, S. Sukhwinder Singh, P Gregory, P Rahul & H. W. Eugene. (2014). Epithelial-mesenchymal transition as a fundamental underlying pathogenic process in COPD airways: fibrosis, remodeling and cancer. Expert Rev Respir Med, 8(5), 547-559. https://doi.org/10.1586/17476348.2014.948853
  23. D. Bartis, N. Mise, R. Y. Mahida, O. Eickelberg & D. R. Thickett. (2014). Epithelial- mesenchymal transition in lung development and disease: does it exist and is it important? Thorax, 69, 760-65. https://doi.org/10.1136/thoraxjnl-2013-204608
  24. Q. Wang, Y. Wang, Y. Zhang, Y. Zhang & W. Xiao. (2013). The role of uPAR in epithelial-mesenchymal transition in small airway epithelium of patients with chronic obstructive pulmonary disease. Respir. Res, 14, 67. https://doi.org/10.1186/1465-9921-14-67