AI Article Synopsis

  • The bladder wall is impacted by pressure changes during filling and voiding, leading to an imbalance of MMPs and TIMPs that can cause bladder issues.
  • A study examined how β-adrenoceptor signaling affects MMP and TIMP expression in human urothelial cells when exposed to high pressure, revealing downregulation of MMP1 and MMP2 and upregulation of TIMP1.
  • Agonists of β-adrenoceptors increased MMP expression, while PKA signaling modulated this effect, suggesting a potential therapeutic target for conditions like partial bladder outlet obstruction.

Article Abstract

The bladder wall is constantly subjected to intravesical pressure during the filling and voiding cycles. An imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) under elevated intravesical pressure contributes to pathological changes in the bladder. To investigate the changes in human urothelial cells (HUCs) under elevated intravesical pressure, this study analyzed the effect of β-adrenoceptor signaling on the expression of MMPs and TIMPs in HUCs exposed to pathological hydrostatic pressure (HP) (70 cm H O) for 6 hours. Quantitative polymerase chain reaction, Western blot analysis, and cell fluorescence staining were used to explore the effect of β-adrenoceptor signaling on the expression of MMPs and TIMPs in HUCs after agonist and/or antagonist treatment. The expression levels of β - and β -adrenoceptor, MMP1, and MMP2 were greatly downregulated, while the expression of TIMP1 was greatly upregulated. Formoterol and BRL 37344, which are agonists of β - and β -adrenoceptor, respectively, significantly increased MMP1 and MMP2 expression under 70 cm H O. As a classic downstream pathway of β - and β -adrenoceptor, protein kinase A (PKA) signaling inhibited MMP1 and MMP2 expression by regulating cAMP response element binding protein (CREB) activity. MMP1 and MMP2 expression in HUCs under 70 cm H O was modified by β - and β -adrenoceptor via the PKA/CREB pathway. This outcome suggests that MMPs likely participate in the pathological effects of elevated intravesical pressure. The underlying mechanism of β - and β -adrenoceptor in elevated intravesical pressure was also revealed; this mechanism constitutes a new potential therapeutic target for partial bladder outlet obstruction.

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http://dx.doi.org/10.1002/nau.24362DOI Listing

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