MMP9 overexpression is associated with good surgical outcome in children with UPJO: Preliminary results

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Citações na Scopus
4
Tipo de produção
article
Data de publicação
2016
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ISSN da Revista
Título do Volume
Editora
BIOMED CENTRAL LTD
Citação
BMC UROLOGY, v.16, article ID 44, 5p, 2016
Projetos de Pesquisa
Unidades Organizacionais
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Resumo
Background: Ureteropelvic junction obstruction (UPJO) diagnosed prenatally occurs in 1: 150 -1: 1200 pregnancies. Although many studies investigating the molecular changes of this obstructed segment have been performed, the underlying mechanisms are still unclear. The role of extracellular matrix (ECM) components remains controversial, and the investigations in the field of ECM changes, might help the better understanding of the pathogenesis of this common condition. The aim of the present study was to investigate for the first time in the literature whether MMP9 and its specific inhibitors, TIMP1 and RECK, are expressed in a reproducible, specific pattern in UPJ. Methods: UPJO specimens were obtained from 16 children at the time of dismembered pyeloplasty due to intrinsic UPJ stenosis. Expression levels of the three genes (MMP9, TIMP1 and RECK) were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Then correlated the expression levels of the genes according to grade study population that was divided in 2 categories according to Society of Fetal Urology classification, grade 3 (moderate) and 4 (severe). For DTPA we subdivided the childrens in 2 groups, obstructive (T 1/2 more than 20 min) and partial obstructive (T 1/2 between 10 and 20 min) and success in a surgery was defined as decrease in T 1/ 2 to less than 20 min, absence of symptoms, improving renal function and decreasing dilatation on successive exams. Results: MMP9 was underexpressed and TIMP1 and RECK were overexpressed in children with obstructive DTPA but the differences were not statistically significant. Overexpression of MMP9 was higher among patients with severe grade of UPJ compared to those with moderate grade. Surprisingly expression levels of MMP-9 was three times higher in children who were successfully treated by surgery (n = 10) (p = 0.072), so those who were followed for at least 1 year after surgery and remained with improvement in renal function and decreasing dilation on intravenous urogram and TIMP-1 was underexpressed in 100 % of this cases (p = 0.00). Conclusions: We showed an increase in expression of MMP9 and a decrease in expression of TIMP1 in children who improving renal function and decreasing dilation after surgery. We believe that the higher expression of MMP9 in these cases can reflect an increase in degradation and remodeling process that could be used as a marker for surgical outcome.
Palavras-chave
UPJO, Metaloproteinases, Children
Referências
  1. Carr MC, 2007, CAMPBELL WALSH UROLO, P3359
  2. Chevalier RL, 2002, KIDNEY INT, V61, P2033, DOI 10.1046/j.1523-1755.2002.00359.x
  3. Choi YJ, 2000, KIDNEY INT, V58, P1481, DOI 10.1046/j.1523-1755.2000.00310.x
  4. Elder JS, 1997, PEDIATR CLIN N AM, V44, P1299, DOI 10.1016/S0031-3955(05)70558-7
  5. Gawlowska A, 2003, PRZEGL PEDIAT, V33, P282
  6. JOHNSTON JH, 1977, J UROLOGY, V117, P97
  7. Kim WJ, 2000, J UROLOGY, V163, P1271, DOI 10.1016/S0022-5347(05)67759-2
  8. Koleda P, 2012, INT UROL NEPHROL, V44, P7, DOI 10.1007/s11255-011-9970-5
  9. Lang RJ, 2006, J PHYSIOL-LONDON, V576, P695, DOI 10.1113/jphysiol.2006.116855
  10. LEE BR, 1992, J UROLOGY, V148, P1482
  11. Lee RS, 2006, PEDIATRICS, V118, P586, DOI 10.1542/peds.2006-0120
  12. Matsui Y, 1998, SPINE, V23, P863, DOI 10.1097/00007632-199804150-00005
  13. Mendelsohn C, 2004, J CLIN INVEST, V113, P957, DOI 10.1172/JCI21402
  14. Murakumo M, 1997, J UROLOGY, V157, P1963, DOI 10.1016/S0022-5347(01)64910-3
  15. Oswald J, 2004, J UROLOGY, V172, P1099, DOI 10.1097/01.ju.0000135673.28496.70
  16. Silva AC S e, 2014, DIS MARKERS, V2014
  17. Solari V, 2003, J UROLOGY, V170, P2420, DOI 10.1097/01.ju.0000097401.03293.f0
  18. Toi M, 1998, BREAST CANCER RES TR, V52, P113, DOI 10.1023/A:1006167202856
  19. Vos CMP, 2000, EXP NEUROL, V163, P324, DOI 10.1006/exnr.2000.7388
  20. Zhang PL, 2000, PEDIATR NEPHROL, V14, P820