Characterization of global and region‐specific transcriptomic alterations in the bladder following acute partial bladder outlet obstruction in female mini‐swine

Abstract

Partial bladder outlet obstruction (pBOO) is a fibroproliferative disorder that results in poorly compliant, high‐pressure bladders due to lower urinary tract occlusion. The mechanisms governing pBOO‐induced bladder remodeling remain poorly understood. The goals of the present study were to profile global and region‐specific transcriptomes of porcine bladders in response to pBOO using RNA sequencing and to identify genes and pathways differentially affected in the bladder dome and trigone by obstructive injury. Nine adult female Yucatan mini‐swine were randomized and divided into either nonsurgical controls ( n  = 5) or those subjected to pBOO for 4 weeks ( n  = 4). Post‐pBOO swine demonstrated bladder smooth muscle hypertrophy as well as significant declines in bladder capacity (35% ± 7% of baseline) and compliance (38% ± 10% of baseline). The global transcriptome of obstructed bladders revealed enrichment of processes related to loss of urothelial barrier function, immune activation, cell cycle regulation, extracellular matrix organization, and signal transduction similar to human and rodent evaluations of pBOO. Moreover, our data also showed that adaptive responses to pBOO are regionally dependent rather than globally uniform, with zonal‐specific divergence observed across hypoxic, fibrotic, metabolic, and neuronal pathways between the obstructed dome and trigone. These results highlight the regional heterogeneity of bladder responses to obstructive urologic disease.