The association between impaired autophagy and the development of congenital ureteropelvic junction obstruction.

Abstract

To investigate the association between impaired autophagy in smooth muscle cells and the development of congenital ureteropelvic junction (UPJ) obstruction (UPJO). 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. 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. In conclusion, impaired autophagy is associated with the development of congenital UPJO. Nonetheless, further studies are mandated to establish its etiologic role.