title: MMP9 overexpression is associated with good surgical outcome in children with UPJO: Preliminary results.
abstract: 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.
authors.affiliation: Urology Department, Laboratory of Medical Investigation (LIM55), University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2° floor, room 2145, 01246-903, Sao Paulo, Brazil. sasareis@gmail.com.
authors.forename: Sabrina Thalita
authors.initials: ST
authors.lastname: Reis
authors.affiliation: Urology Department, Laboratory of Medical Investigation (LIM55), University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2° floor, room 2145, 01246-903, Sao Paulo, Brazil.
authors.forename: Kátia R M
authors.initials: KRM
authors.lastname: Leite
authors.affiliation: Urology Department, Laboratory of Medical Investigation (LIM55), University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2° floor, room 2145, 01246-903, Sao Paulo, Brazil.
authors.forename: Nayara Izabel
authors.initials: NI
authors.lastname: Viana
authors.affiliation: Urology Department, Laboratory of Medical Investigation (LIM55), University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2° floor, room 2145, 01246-903, Sao Paulo, Brazil.
authors.forename: Roberto Iglesias
authors.initials: RI
authors.lastname: Lopes
authors.affiliation: Urology Department, Laboratory of Medical Investigation (LIM55), University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2° floor, room 2145, 01246-903, Sao Paulo, Brazil.
authors.forename: Caio Martins
authors.initials: CM
authors.lastname: Moura
authors.affiliation: Urology Department, Laboratory of Medical Investigation (LIM55), University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2° floor, room 2145, 01246-903, Sao Paulo, Brazil.
authors.forename: Renato F
authors.initials: RF
authors.lastname: Ivanovic
authors.affiliation: Urology Department, Laboratory of Medical Investigation (LIM55), University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2° floor, room 2145, 01246-903, Sao Paulo, Brazil.
authors.forename: Marcos
authors.initials: M
authors.lastname: Machado
authors.affiliation: Urology Department, Laboratory of Medical Investigation (LIM55), University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2° floor, room 2145, 01246-903, Sao Paulo, Brazil.
authors.forename: Francisco Tibor
authors.initials: FT
authors.lastname: Denes
authors.affiliation: Urology Department, Laboratory of Medical Investigation (LIM55), University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2° floor, room 2145, 01246-903, Sao Paulo, Brazil.
authors.forename: Amilcar
authors.initials: A
authors.lastname: Giron
authors.affiliation: Urology Department, Laboratory of Medical Investigation (LIM55), University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2° floor, room 2145, 01246-903, Sao Paulo, Brazil.
authors.forename: William Carlos
authors.initials: WC
authors.lastname: Nahas
authors.affiliation: Urology Department, Laboratory of Medical Investigation (LIM55), University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2° floor, room 2145, 01246-903, Sao Paulo, Brazil.
authors.forename: Miguel
authors.initials: M
authors.lastname: Srougi
authors.affiliation: Urology Department, Laboratory of Medical Investigation (LIM55), University of Sao Paulo Medical School, Av. Dr. Arnaldo 455, 2° floor, room 2145, 01246-903, Sao Paulo, Brazil.
authors.forename: Carlo C
authors.initials: CC
authors.lastname: Passerotti
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D058851:GPI-Linked Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007223:Infant; D007682:Kidney Pelvis; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis* / Q000235:genetics; D016896:Treatment Outcome; D014517:Ureteral Obstruction / Q000235:genetics / Q000601:surgery*
chemical_list: D058851:GPI-Linked Proteins; C115460:RECK protein, human; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9
keywords: Children; Metaloproteinases; UPJO