Near-Normalized Gene Expression Profiles in Bladder With Detrusor Overactivity in Rats With Bladder Outlet Obstruction After Deobstruction

Abstract

PurposeThe pathophysiological role of detrusor overactivity (DO) in the bladder, which is commonly observed in various bladder diseases, is not well understood. DO appears in bladder outlet obstruction (BOO), and may continue even after subsequent deobstruction. DO therefore provides an excellent opportunity to observe molecular biological changes.MethodsIn this study, to understand the molecular effects of persistent DO after BOO induction and deobstruction, we performed awake cystometry on female Sprague-Dawley rats divided into 4 groups: a sham group, a BOO group, a deobstructed group with DO after BOO (DDO), and a deobstructed group without DO after BOO (non-DDO). Total RNA was extracted from the bladder samples, and gene expression profiles were compared between the sham and model groups.ResultsDO was observed in 5 of the 6 rats (83%) in the BOO group, and in 6 of the 13 rats (46%) in the deobstructed group. The non-DDO group showed a significantly greater residual volume than the DDO group. Through a clustering analysis of gene expression profiles, we identified 7,532 common upregulated and downregulated genes, the expression of which changed by more than 2 fold. In the BOO group, 898 upregulated and 2,911 downregulated genes were identified. The non-DDO group showed 3,472 upregulated and 4,025 downregulated genes, whereas in the DDO group, only 145 and 72 genes were upregulated and downregulated, respectively.ConclusionsAbnormal function and gene expression profiles in bladders after BOO were normalized in the BOO rats with DO after deobstruction, whereas in those without DO, abnormal function persisted and the gene expression profile became more abnormal. DO may play a protective role against the stress to the bladder induced by BOO and deobstruction as a form of adaptive neuroplasticity.

Gene Expression Profiles During Tissue Remodeling Following Bladder Outlet Obstruction

“…The results showed that many of the genes were categorized into the molecular functions category, including cytokines and cytokine receptors (Fig. 2B), consistent with the results of previous studies using BOO model rats 4,16 .…”

“…In the decompensation stage, loss of smooth muscle, deposition of extracellular matrix, and degradation of neurons occur under the sustained stress caused by obstruction. In each stage of the bladder remodeling, several signaling pathways are modulated in the various compartments of the bladder in animal models of BOO and human patients with BOO 3,4 . Alterations in gene expression at the initiation of bladder remodeling play important roles as triggers of disease progression.…”

Carbon monoxide–releasing molecule-3: Amelioration of renal ischemia reperfusion injury in a rat model

“…There have been several efforts in the urology field to elucidate the genes related to the IRI pathway [21]. Toll-like receptors, sphingosine-1-phosphate receptors, and hypoxiainducible factors have been reported to worsen tubular epithelial cell function, eventually causing acute renal damage, delayed graft function, and ultimately acute-on-chronic rejection [22].…”

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“…Already research studies revealed that C. obtusa has anti-inflammatory effect (Kim et al, 2015; Rufino et al, 2014). Inflammation is on action for a variety of reason (Lee et al, 2017; Park et al, 2018; Song et al, 2017). If inflammation action in the skin, it can be various reactions such as increase of blood flow blood flow increase, cell metabolism enhancement, vasodilation to defend and recover (Ferrero-Miliani et al, 2007).…”