title: The association between impaired autophagy and the development of congenital ureteropelvic junction obstruction.
abstract: OBJECTIVE
  To investigate the association between impaired autophagy in smooth muscle cells and the development of congenital ureteropelvic junction (UPJ) obstruction (UPJO).
  
  
  METHODS
  Tissue specimens were obtained from 40 patients with unilateral UPJO and were divided into 3 sections as renal pelvis, site of obstruction, and the ureter distal to obstruction. Control specimens were obtained from the UPJ of 40 age-matched cadavers. Autophagy was evaluated by image analysis techniques for the expression of light chain 3 (LC3) after immunohistochemical staining of LC3 rabbit polyclonal antibody and Western blot analysis; additionally, myocyte apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, 4',6-diamidino-2-phenylindole staining, and p53 immunohistochemical staining. To assess the possible role of cell senescence, P21 and P16 immunohistochemistry staining was applied. Cellular proliferation was assessed by image analysis of proliferating cell nuclear antigen-stained specimens.
  
  
  RESULTS
  LC3 expression was significantly increased at the renal pelvis (P <.05). Apoptotic indices of smooth muscle cells and Bcl-2 were significantly greater at the site of UPJO (5.15 ± 0.91) compared with the UPJs of the control group (P <.001). A significant negative correlation was found between TUNEL and LC3 in all sections of the obstructed UPJ complex (P <.05). Proliferating cell nuclear antigen and LC3 were positively correlated in the renal pelvis and UPJ (P <.05); however, no specimen was stained for p16, p21, and p53.
  
  
  CONCLUSIONS
  In conclusion, impaired autophagy is associated with the development of congenital UPJO. Nonetheless, further studies are mandated to establish its etiologic role.
authors.affiliation: Division of Pediatric Urology, Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, MD.
authors.forename: Ali
authors.initials: A
authors.lastname: Tourchi
authors.affiliation: Department of Pediatric Urology, Pediatric Urology Research Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: kajbafzd@sina.tums.ac.ir.
authors.forename: Abdol-Mohammad
authors.initials: AM
authors.lastname: Kajbafzadeh
authors.affiliation: Department of Pediatric Urology, Pediatric Urology Research Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ebadi
authors.affiliation: Department of Pathology, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Tavangar
authors.affiliation: Department of Pediatric Urology, Pediatric Urology Research Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Neda
authors.initials: N
authors.lastname: Jarooghi
mesh_terms: D000704:Analysis of Variance; D001343:Autophagy; D001707:Biopsy, Needle; D015153:Blotting, Western; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007223:Infant; D007682:Kidney Pelvis / Q000473:pathology*; D008297:Male; D008856:Microscopy, Fluorescence; D009130:Muscle, Smooth / Q000473:pathology*; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D014517:Ureteral Obstruction / Q000151:congenital / Q000473:pathology*