Urethral meatus stricture BOO stimulates bladder smooth muscle cell proliferation and pyroptosis via IL‑1β and the SGK1‑NFAT2 signaling pathway

Abstract

Bladder outlet obstruction (Boo), which is primarily caused by benign prostatic hyperplasia, is a common chronic disease. However, previous studies have most commonly investigated Boo using the acute obstruction model. in the present study, a chronic obstruction model was established to investigate the different pathological alterations in the bladder between acute and chronic obstruction. compared with chronic obstruction, acute obstruction led to increased expression of proliferating cell nuclear antigen and interleukin-1β, which are markers of proliferation and inflammation, respectively. Furthermore, increased fibrosis in the bladder at week 2 was observed. Low pressure promoted mice bladder smooth muscle cell (MBSMc) proliferation, and pressure overload inhibited cell proliferation and increased the proportion of dead MBSMCs. Further investigation using serum/glucocorticoid regulated kinase 1 (SGK1) small interfering rnas indicated that low pressure may promote MBSMc proliferation by upregulating SGK1 and nuclear factor of activated T-cell expression levels. Therefore, the present study suggested that acute obstruction led to faster decompensation of bladder function and chronic bladder obstruction displayed an enhanced ability to progress to Boo.

Serum/glucocorticoid‐regulated kinase 1‐targeted transient receptor potential oxalate subtype 1 regulates bladder smooth muscle cell proliferation due to bladder outlet obstruction in mice via activated T cell nuclear factor transcription factor 2

“…A large number of studies have shown that in the pathophysiological process of bladder remodeling, increased intravesical pressure, which is mechanical stress, is an important stimulator of hypertrophy and the proliferation of bladder wall muscle layer cells. 10 , 28 Our previous studies have shown that a hydrostatic pressure of 200 cm H 2 O can promote the proliferation of MBSMCs, which is achieved through the SGK1‐NFAT2 signaling pathway, 11 but unfortunately, no specific connection between these two factors has been found. Therefore, this study further explored the specific mechanism by which the SGK1‐NFAT2 signaling pathway mediates MBSMC proliferation in vivo and in vitro.…”

“…In addition, many studies have shown that NFAT2 plays an important role in promoting cell proliferation 8,9 . Previous research showed that circulating hydrodynamic pressure promotes the proliferation of human BSMCs (HBSMCs) cultured on scaffolds through the PI3K/SGK1 signaling pathway, 10 and BOO promotes the proliferation of bladder smooth muscle cells through the SGK1‐NFAT2 signaling pathway in mice 11 …”

“…8,9 Previous research showed that circulating hydrodynamic pressure promotes the proliferation of human BSMCs (HBSMCs) cultured on scaffolds through the PI3K/SGK1 signaling pathway, 10 and BOO promotes the proliferation of bladder smooth muscle cells through the SGK1-NFAT2 signaling pathway in mice. 11 As a member of the transient receptor potential (TRP) family, the transient receptor potential vanilloid (TRPV) channel is a tetrameric protein channel that is widely distributed in the human body and can allow Ca 2+ , Mg 2+ , and Na + and variety of cations, such as K + , to pass through, and plays an important role in cell function and signal pathway transmission. 12,13 There are six members in the TRPV subfamily.…”

Pathophysiological Mechanisms Involved in Overactive Bladder/Detrusor Overactivity

“…With BOO, micturition causes cyclical ischemia, followed by repeated reperfusion that generates free radicals and ultimately tissue injury, cytokine release and inflammation [40•]. Hypoxia of the bladder wall is evidenced by increases in hypoxia-inducible factor (HIF) and inflammatory responses are initiated by elevated levels of pro-inflammatory cytokines including interleukin-1β (IL-1β) and transforming growth factor-β (TGF-1 β) [39,41]. Recent studies have identified toll-like receptors (TLR-4 and TLR-9) involved in the induction of inflammation, with the expression of both these receptors increased in the urothelium of animals with BOO.…”

CircRNA/miRNA/mRNA axis participates in the progression of partial bladder outlet obstruction

“…Partial bladder outlet obstruction (pBOO) is a common urinary disease, which is commonly seen in clinical benign prostatic hyperplasia (BPH), bladder neck contracture, urethral stricture, congenital urethral malformation and bladder neck tumor, among which BPH is the most common cause of pBOO [ 1 – 3 ]. Studies have shown that pBOO is the initiating factor of the physiological and pathological cascade that leads to deep changes in the structure and function of the bladder [ 4 ].…”