Progressive bladder remodeling due to bladder outlet obstruction: a systematic review of morphological and molecular evidences in humans

BACKGROUND Bladder outlet obstruction is a common urological condition. We aimed to summarize available evidences about bladder outlet obstruction-induced molecular and morphological alterations occurring in human bladder. METHODS We performed a literature search up to December 2017 including clinical and preclinical basic research studies on humans. The following search terms were combined: angiogenesis, apoptosis, bladder outlet obstruction, collagen, electron microscopy, extracellular matrix, fibrosis, hypoxia, histology, inflammation, innervation, ischemia, pressure, proliferation, remodeling, suburothelium, smooth muscle cells, stretch, urothelium. RESULTS We identified 36 relevant studies. A three-stages model of bladder wall remodeling can be hypothesized involving an initial hypertrophy phase, a subsequent compensation phase and a later decompensation. Histological and molecular alterations occur in the following compartments: urothelium, suburothelium, detrusor smooth muscle cells, detrusor extracellular matrix, nerves. Cyclic stretch, increased hydrostatic and cyclic hydrodynamic pressure and hypoxia are stimuli capable of modulating multiple signaling pathways involved in this remodeling process. CONCLUSIONS Bladder outlet obstruction leads to progressive bladder tissue remodeling in humans. Multiple signaling pathways are involved.