Moderated Poster

Poster, Podium & Video Sessions

MP94-11: AUTOPHAGY, APOPTOSIS AND CELL PROLIFERATION IN EXTROPHY-EPISPADIAS COMPLEX

Tuesday, May 16
7:00 AM - 9:00 AM
Location: BCEC: Room 253AB

Presentation Authors: Mahsa Shabaninia*, Ali Tourchi, Heather Di Carlo, John Gearhart, Baltimore, MD

Introduction: Very few pathophysiological mechanisms have been proposed as the etiology of bladder exstrophy (BE). Autophagy, or type II programmed cell death pathway, is an evolutionary conserved process involving intracellular degradation and recycling of cytoplasmic organelles. A basal level of autophagy is detected in most tissues, maintaining cellular homeostasis and viability through development and differentiation of eukaryotic organisms. Impairment of protein degradation pathways such as autophagy has been described in disorders relating to several organs and tissues including, neural defects acute, diseases of skeletal and cardiac muscles, and congenital ureteropelvic junction obstruction. However, it&[prime]s alteration in bladder smooth muscle cells of BE patients has not yet been reported. Herein, the authors investigated the state of autophagy and its interactions with cells apoptosis and proliferation in patients with BE.

Methods: Primary cultures of bladder smooth muscle cells were established from patients with successful neonatal bladder closure (group 1, N=5), delayed closure due to small bladder template (group 2, N=5) and vesicoureteral reflux as control (group3, N=5). The myogenicity of the cultures was determined using anti-desmin antibody. Immunofluorescence staining for LC3 was used to detect autophagy. Cells apoptosis was assessed using TUNEL assay, 4&[prime], 6-diamidino-2-phenylindole staining. Cellular proliferation was assessed by image analysis of immunofluorescence staining for Ki-67.

Results: Immunohistochemical staining revealed consistent positivity (greater than 95%) for Desmin in all cultures that confirms the myogenicity of them. Apoptosis was significantly higher in delayed closure group compared to other groups. Autophagy marker (LC3) was more expressed in delayed closure group compared to the other groups. Cellular proliferation was significantly lower in delayed closure group compared with control and successful neonatal closure groups.


Conclusions: Our results confirms that there are distinct differences in bladder smooth muscle cell function between control, successful neonatal closure and delayed closure cases due to small bladder template which persist in culture. Children with slower bladder growth and small bladder templates showed up-regulated autophagic process and increased apoptotic indices while experiencing a dramatic decrease in their bladder smooth muscle cells proliferation. Finally the concept of manipulating autophagy may lead to promising outcomes for BE patients in future.

Source Of Funding: None

Mahsa Shabaninia

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MP94-11: AUTOPHAGY, APOPTOSIS AND CELL PROLIFERATION IN EXTROPHY-EPISPADIAS COMPLEX



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