12 / 492
13:48 - 13:51
S1-7
(PP)
THE IMPACT OF AUTOPHAGY IN NEUROPATHIC BLADDER REMODELING
Souzan SALEMI
1
, Maya HORST
2
, Rita GOBET
2
, Tullio SULSER
3
and Daniel EBERLI
4
1) University Hospital Zürich, Urology, Zürich, SWITZERLAND - 2) Division of Pediatric Urology, Children's Hospital
Zurich, Pediatric Surgery, Zürich, SWITZERLAND - 3) University Hospital Zurich, Urology, Zürich, SWITZERLAND - 4)
University Hospital Zurich, Urology, Zürich, SWITZERLAND
PURPOSE
Neurogenic bladder dysfunction is the result of disease or injury to the neural pathways and commonly occurs in
patients with meningomyelocele or after spinal cord injury. During the pathogenesis the smooth muscle cells (SMC) shift
from contractile SMC phenotype towards a synthetic type. In muscular disorders increased autophagy is known to
protect cells from deterioration by compensating for defects in lysosome function. However, the accumulation of
autophagosomes can also impair cell function over time. Autophagy may play an important role in remodeling of bladder
SMC in children with neuropathic bladder. In this study we investigated the role of autophagy in neuropathic bladders in
the pediatric population.
MATERIAL AND METHODS
Full thickness bladder biopsies were taken from children with neuropathic disorder. Samples obtained from healthy
donors without urological problems were used as control. A piece of bladder tissue was snap frozen for genetic analysis
and another piece was fixed for immunostaining. Samples were stained with SMC lineage associated markers calponin,
smoothelin, α-SMA and autophagy proteins LC3, Atg5 and Beclinl. In addition the expression of autophagy genes and
proteins were investigated by real time PCR and Western blot analysis.
RESULTS
We found that the ATG5 gene, a key regulator of autophagy, is upregulated in neuropathic muscle tissue compared with
normal bladder. At protein level increased ATG5 protein was repetitively shown in WB and immunostaining. Neuropathic
bladder muscle exhibited a punctated immunostaining pattern for LC3 in subset of SM confirming accumulation of
autophagosomes. Pronounced elevation of ATG5 in SM in neuropathic bladder tissue co-localized with a downregulation
of the key contractile proteins smoothelin and calponin.
CONCLUSIONS
Our study reveals that autophagy is important factor in the remodeling of SMC and functionality of bladder SM tissue in
neuropathic bladder. Since autophagy can be influenced by oral medication this research might lead to novel strategies
preventing the remodeling and deterioration of neuropathic bladder muscle tissues.