DOI QR코드

DOI QR Code

Low levels of tissue inhibitor of metalloproteinase-2 at birth may be associated with subsequent development of bronchopulmonary dysplasia in preterm infants

  • Lee, Choae (Graduate School, CHA University) ;
  • An, Jaewoo (Department of Pediatrics, CHA University Bundang Medical Center) ;
  • Kim, Ji Hee (Department of Pediatrics, CHA University Gangnam Medical Center) ;
  • Kim, Eun Sun (Department of Pediatrics, Kangwon National University School of Medicine) ;
  • Kim, Soo Hyun (CHA University School of Medicine) ;
  • Cho, Yeon Kyung (CHA University School of Medicine) ;
  • Cha, Dong Hyun (CHA University School of Medicine) ;
  • Han, Man Yong (Department of Pediatrics, CHA University Bundang Medical Center) ;
  • Lee, Kyu Hyung (Department of Pediatrics, CHA University Bundang Medical Center) ;
  • Sheen, Youn Ho (Department of Pediatrics, CHA University Gangnam Medical Center)
  • 투고 : 2015.03.09
  • 심사 : 2015.08.20
  • 발행 : 2015.11.15

초록

Purpose: Bronchopulmonary dysplasia (BPD) is characterized by inflammation with proteolytic damage to the lung extracellular matrix. The results from previous studies are inconsistent regarding the role of proteinases and antiproteinases in the development of BPD. The aim of the present study was to investigate whether matrix metalloproteinase (MMP)-8, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, and TIMP-1 levels in the serum of preterm infants at birth are related to the development of BPD. Methods: Serum was collected from 62 preterm infants at birth and analyzed for MMP-8, MMP-9, TIMP-2, and TIMP-1 by using enzyme-linked immunosorbent assay. MMPs and TIMPs were compared in BPD (n=24) and no BPD groups (n=38). Clinical predictors of BPD (sex, birth weight, gestational age, etc.) were assessed for both groups. The association between predictors and outcome, BPD, was assessed by using multivariate logistic regression. Results: Sex, birth weight, and mean gestational age were similar between the groups. BPD preterm infants had significantly lower TIMP-2 levels at birth compared with no BPD preterm infants ($138.1{\pm}23.0ng/mL$ vs. $171.8{\pm}44.1ng/mL$, P=0.027). No significant difference was observed in MMP-8, MMP-9, and TIMP-1 levels between the two groups. Multivariate logistic regression analysis indicated that the TIMP-2 levels were predictive of BPD after adjusting for sex, birth weight, gestational age, proteinuric preeclampsia, and intraventricular hemorrhage (${\beta}=-0.063$, P=0.041). Conclusion: Low TIMP-2 serum levels at birth may be associated with the subsequent development of BPD in preterm infants.

키워드

참고문헌

  1. Hahn WH, Chang JY, Chang YS, Shim KS, Bae CW. Recent trends in neonatal mortality in very low birth weight Korean infants: in comparison with Japan and the USA. J Korean Med Sci 2011;26:467-73. https://doi.org/10.3346/jkms.2011.26.4.467
  2. Choi CW, Kim BI, Kim EK, Song ES, Lee JJ. Incidence of bronchopulmonary dysplasia in Korea. J Korean Med Sci 2012;27:914-21. https://doi.org/10.3346/jkms.2012.27.8.914
  3. Schmidt B, Roberts R, Millar D, Kirpalani H. Evidence-based neonatal drug therapy for prevention of bronchopulmonary dysplasia in very-low-birth-weight infants. Neonatology 2008;93:284-7. https://doi.org/10.1159/000121453
  4. Ekekezie II, Thibeault DW, Simon SD, Norberg M, Merrill JD, Ballard RA, et al. Low levels of tissue inhibitors of metalloproteinases with a high matrix metalloproteinase-9/tissue inhibitor of metalloproteinase-1 ratio are present in tracheal aspirate fluids of infants who develop chronic lung disease. Pediatrics 2004;113:1709-14. https://doi.org/10.1542/peds.113.6.1709
  5. Cederqvist K, Sorsa T, Tervahartiala T, Maisi P, Reunanen K, Lassus P, et al. Matrix metalloproteinases-2, -8, and -9 and TIMP-2 in tracheal aspirates from preterm infants with respiratory distress. Pediatrics 2001;108:686-92. https://doi.org/10.1542/peds.108.3.686
  6. Fukunaga S, Ichiyama T, Maeba S, Okuda M, Nakata M, Sugino N, et al. MMP-9 and TIMP-1 in the cord blood of premature infants developing BPD. Pediatr Pulmonol 2009;44:267-72. https://doi.org/10.1002/ppul.20993
  7. Chakraborti S, Mandal M, Das S, Mandal A, Chakraborti T. Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem 2003;253:269-85. https://doi.org/10.1023/A:1026028303196
  8. Kheradmand F, Rishi K, Werb Z. Signaling through the EGF receptor controls lung morphogenesis in part by regulating MT1-MMP-mediated activation of gelatinase A/MMP2. J Cell Sci 2002;115(Pt 4):839-48.
  9. Dufour A. Degradomics of matrix metalloproteinases in inflammatory diseases. Front Biosci (Schol Ed) 2015;7:150-67. https://doi.org/10.2741/430
  10. Marchesi C, Dentali F, Nicolini E, Maresca AM, Tayebjee MH, Franz M, et al. Plasma levels of matrix metalloproteinases and their inhibitors in hypertension: a systematic review and meta-analysis. J Hypertens 2012;30:3-16. https://doi.org/10.1097/HJH.0b013e32834d249a
  11. Catalan V, Gomez-Ambrosi J, Rodriguez A, Fruhbeck G. Role of extracellular matrix remodelling in adipose tissue pathophysiology: relevance in the development of obesity. Histol Histopathol 2012;27:1515-28.
  12. Nolan A, Kwon S, Cho SJ, Naveed B, Comfort AL, Prezant DJ, et al. MMP-2 and TIMP-1 predict healing of WTC-lung injury in New York City firefighters. Respir Res 2014;15:5. https://doi.org/10.1186/1465-9921-15-5
  13. Roy R, Yang J, Moses MA. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol 2009;27:5287-97. https://doi.org/10.1200/JCO.2009.23.5556
  14. Iyer RP, Patterson NL, Fields GB, Lindsey ML. The history of matrix metalloproteinases: milestones, myths, and misperceptions. Am J Physiol Heart Circ Physiol 2012;303:H919-30. https://doi.org/10.1152/ajpheart.00577.2012
  15. Nagase H. Activation mechanisms of matrix metalloproteinases. Biol Chem 1997;378:151-60.
  16. O'Connor CM, FitzGerald MX. Matrix metalloproteases and lung disease. Thorax 1994;49:602-9. https://doi.org/10.1136/thx.49.6.602
  17. Ohbayashi H. Matrix metalloproteinases in lung diseases. Curr Protein Pept Sci 2002;3:409-21. https://doi.org/10.2174/1389203023380549
  18. Fligiel SE, Standiford T, Fligiel HM, Tashkin D, Strieter RM, Warner RL, et al. Matrix metalloproteinases and matrix metalloproteinase inhibitors in acute lung injury. Hum Pathol 2006;37:422-30. https://doi.org/10.1016/j.humpath.2005.11.023
  19. Kong MY, Gaggar A, Li Y, Winkler M, Blalock JE, Clancy JP. Matrix metalloproteinase activity in pediatric acute lung injury. Int J Med Sci 2009;6:9-17.
  20. Hartog CM, Wermelt JA, Sommerfeld CO, Eichler W, Dalhoff K, Braun J. Pulmonary matrix metalloproteinase excess in hospitalacquired pneumonia. Am J Respir Crit Care Med 2003;167:593-8. https://doi.org/10.1164/rccm.200203-258OC
  21. Schaaf B, Liebau C, Kurowski V, Droemann D, Dalhoff K. Hospital acquired pneumonia with high-risk bacteria is associated with increased pulmonary matrix metalloproteinase activity. BMC Pulm Med 2008;8:12. https://doi.org/10.1186/1471-2466-8-12
  22. Obase Y, Rytila P, Metso T, Pelkonen AS, Tervahartiala T, Turpeinen M, et al. Effects of inhaled corticosteroids on metalloproteinase-8 and tissue inhibitor of metalloproteinase-1 in the airways of asthmatic children. Int Arch Allergy Immunol 2010;151:247-54. https://doi.org/10.1159/000242362
  23. Murphy G. Tissue inhibitors of metalloproteinases. Genome Biol 2011;12:233. https://doi.org/10.1186/gb-2011-12-11-233
  24. Sweet DG, Curley AE, Chesshyre E, Pizzotti J, Wilbourn MS, Halliday HL, et al. The role of matrix metalloproteinases -9 and -2 in development of neonatal chronic lung disease. Acta Paediatr 2004;93:791-6. https://doi.org/10.1111/j.1651-2227.2004.tb03020.x
  25. Lukkarinen H, Hogmalm A, Lappalainen U, Bry K. Matrix metalloproteinase- 9 deficiency worsens lung injury in a model of bronchopulmonary dysplasia. Am J Respir Cell Mol Biol 2009;41:59-68. https://doi.org/10.1165/rcmb.2008-0179OC
  26. Schulz CG, Sawicki G, Lemke RP, Roeten BM, Schulz R, Cheung PY. MMP-2 and MMP-9 and their tissue inhibitors in the plasma of preterm and term neonates. Pediatr Res 2004;55:794-801. https://doi.org/10.1203/01.PDR.0000120683.68630.FB
  27. Danan C, Jarreau PH, Franco ML, Dassieu G, Grillon C, Abd Alsamad I, et al. Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia. Am J Physiol Lung Cell Mol Physiol 2002;283:L1086-93. https://doi.org/10.1152/ajplung.00066.2002
  28. Davies PL, Spiller OB, Beeton ML, Maxwell NC, Remold-O'Donnell E, Kotecha S. Relationship of proteinases and proteinase inhibitors with microbial presence in chronic lung disease of prematurity. Thorax 2010;65:246-51. https://doi.org/10.1136/thx.2009.116061
  29. Bejar R, Curbelo V, Coen RW, Leopold G, James H, Gluck L. Diagnosis and follow-up of intraventricular and intracerebral hemorrhages by ultrasound studies of infant's brain through the fontanelles and sutures. Pediatrics 1980;66:661-73.
  30. Pandit PB, O'Brien K, Asztalos E, Colucci E, Dunn MS. Outcome following pulmonary haemorrhage in very low birthweight neonates treated with surfactant. Arch Dis Child Fetal Neonatal Ed 1999;81:F40-4. https://doi.org/10.1136/fn.81.1.F40
  31. Kliegman RM, Walsh MC. Neonatal necrotizing enterocolitis: pathogenesis, classification, and spectrum of illness. Curr Probl Pediatr 1987;17:213-88.
  32. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163:1723-9. https://doi.org/10.1164/ajrccm.163.7.2011060
  33. Lee SJ, Tsang PS, Diaz TM, Wei BY, Stetler-Stevenson WG. TIMP-2 modulates VEGFR-2 phosphorylation and enhances phosphodiesterase activity in endothelial cells. Lab Invest 2010;90:374-82. https://doi.org/10.1038/labinvest.2009.136
  34. Murphy AN, Unsworth EJ, Stetler-Stevenson WG. Tissue inhibitor of metalloproteinases-2 inhibits bFGF-induced human microvascular endothelial cell proliferation. J Cell Physiol 1993;157:351-8. https://doi.org/10.1002/jcp.1041570219
  35. Hoegy SE, Oh HR, Corcoran ML, Stetler-Stevenson WG. Tissue inhibitor of metalloproteinases-2 (TIMP-2) suppresses TKR-growth factor signaling independent of metalloproteinase inhibition. J Biol Chem 2001;276:3203-14. https://doi.org/10.1074/jbc.M008157200

피인용 문헌

  1. Recent advances in our understanding of the mechanisms of late lung development and bronchopulmonary dysplasia vol.313, pp.6, 2017, https://doi.org/10.1152/ajplung.00343.2017
  2. Injured Achilles Tendons Treated with Adipose-Derived Stem Cells Transplantation and GDF-5 vol.7, pp.9, 2015, https://doi.org/10.3390/cells7090127
  3. Differences in Brain-Derived Neurotrophic Factor and Matrix Metalloproteinase-9 between Appropriate Neonates between Normal Birth Weight and Intrauterine Growth Restriction vol.7, pp.5, 2015, https://doi.org/10.3889/oamjms.2019.159
  4. Identification of key pathways and differentially expressed genes in bronchopulmonary dysplasia using bioinformatics analysis vol.42, pp.12, 2015, https://doi.org/10.1007/s10529-020-02986-y