Increased expression of neuregulin 1 in the urothelium of rat bladder with partial bladder outlet obstruction

Abstract

BackgroundThis study determined whether changes in the expression of neuregulin (NRG) 1, erbB2 tyrosine kinase (ErbB2) and the M2 muscarinic receptor in the urothelium and detrusor muscle of the rat bladder were associated with partial bladder outlet obstruction (PBOO).MethodsMale Sprague-Dawley rats (body weight 250–300 g) were used and subdivided into control (n = 10) and PBOO groups (n = 20). PBOO was induced for 21 days, and the expression of NRG1, ErbB2 and M2 muscarinic receptor mRNA and protein was evaluated using reverse transcriptase-polymerase chain reaction (RT-PCR) and western blotting, respectively.ResultsIn the urothelium of rat bladder samples, protein expression and mRNA expression of NRG1, ErbB2 and M2 muscarinic receptor were significantly increased in the PBOO group compared to the control group (p < 0.05). Only mRNA expression levels of NRG1/ ErbB2 were higher in the detrusor muscle of the PBOO group compared to the control group (p < 0.05).ConclusionsOur study demonstrated remarkable changes in the expression of NRG1/ErbB2 receptor mRNA and protein in the urothelium and muscle layer. These results suggest that NRG1 overexpression plays some kind of role against the PBOO-induced upregulated muscarinic receptors in detrusor overactivity.

Changes in the expression and function of the PDE5 pathway in the obstructed urinary bladder

“…It is well known that M 2 and M 3 receptors predominantly modulated the contraction of bladder SM and their dysregulation may lead to change in bladder SM contractility. In line with a previous study in a PBOO rat model 28,29 and BOO patients, 30 our molecular biology experiments demonstrated that M 2 and M 3 receptors were both up‐regulated (at both the mRNA and protein levels) in the PBOO groups, which could be responsible for the increased CC‐induced contraction. Also, carbachol EC50 values were different between PBOO and control (or sham) groups (in Figure 4A,B).…”

Physiological stretch induced proliferation of human urothelial cells via integrin α6‐FAK signaling pathway

“…[9][10][11][12] BOO could significantly change the structure and function of the bladder, resulting in damage to the storage and emptying of the bladder as well as change the morphology and physiological function of the urothelial cells. 16 Urethral epithelium affected nerve activity, detrusor muscle contraction and bladder function by sensing the stimulation of FIGURE 2 Cyclic stretch (5%) increased the expression of integrin α6, FAK and p-FAK (Tyr397). HUCs were exposed to a 24 h stretching cycle as described in supplementary figure S1.…”

“…Current researches on mechanical signal transduction mainly focused on cardiovascular and musculoskeletal system, and many data showed that the proliferation of different cell such as endothelial, muscular, and epithelial cell was regulated by the integrin, FAK signal molecules . BOO could significantly change the structure and function of the bladder, resulting in damage to the storage and emptying of the bladder as well as change the morphology and physiological function of the urothelial cells . Urethral epithelium affected nerve activity, detrusor muscle contraction and bladder function by sensing the stimulation of mechanical and chemical signals .…”