Gynecology II Ward, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan Province, China.
Bioengineered. 2022 Jan;13(1):481-495. doi: 10.1080/21655979.2021.2009417.
Stress urinary incontinence (SUI) is defined as involuntary urinary leakage happening in exertion. Nicotinamide phosphoribosyltransferase (Nampt) is seldom researched in the pathogenesis of SUI. Accordingly, the current study set out to elucidate the role of Nampt in SUI progression. Firstly, we determined Nampt expression patterns in SUI patients and rat models. In addition, fibroblasts were obtained from the anterior vaginal wall tissues of non-SUI patients and subjected to treatment with different concentrations of interleukin-1β (IL-1β), followed by quantification of Nampt expressions in fibroblasts. Subsequently, an appropriate concentration of IL-1β was selected to treat anterior vaginal wall fibroblasts. Nampt was further silenced in IL-1β-treated fibroblasts to assess the role of Nampt in autophagy and extracellular matrix (ECM) degradation. Lastly, functional rescue assays were carried out to inhibit autophagy and evaluate the role of autophagy in the mechanism of Nampt modulating IL-1β-treated fibroblast ECM degradation. It was found that Nampt was highly-expressed in SUI patients and rat models and IL-1β-treated fibroblasts. On the other hand, Nampt silencing was found to suppress ECM degradation and promote SUI fibroblast autophagy. Additionally, inhibition of autophagy attenuated the inhibitory effects of Nampt silencing on SUI fibroblast ECM degradation. Collectively, our findings revealed that Nampt was over-expressed in SUI, whereas Nampt silencing enhanced SUI fibroblast autophagy, and thereby inhibited ECM degradation.
压力性尿失禁（SUI）定义为在用力时发生的不自主的尿液泄漏。烟酰胺磷酸核糖转移酶（Nampt）在 SUI 的发病机制中很少被研究。因此，本研究旨在阐明 Nampt 在 SUI 进展中的作用。首先，我们确定了 Nampt 在 SUI 患者和大鼠模型中的表达模式。此外，我们从非 SUI 患者的前阴道壁组织中获得成纤维细胞，并对其进行不同浓度的白细胞介素-1β（IL-1β）处理，然后定量分析成纤维细胞中的 Nampt 表达。随后，选择适当浓度的 IL-1β 处理前阴道壁成纤维细胞。沉默 IL-1β 处理的成纤维细胞中的 Nampt，以评估 Nampt 在自噬和细胞外基质（ECM）降解中的作用。最后，进行功能挽救实验以抑制自噬，并评估自噬在 Nampt 调节 IL-1β 处理的成纤维细胞 ECM 降解机制中的作用。结果发现，Nampt 在 SUI 患者和大鼠模型以及 IL-1β 处理的成纤维细胞中高表达。另一方面，沉默 Nampt 被发现抑制 ECM 降解并促进 SUI 成纤维细胞自噬。此外，抑制自噬减弱了 Nampt 沉默对 SUI 成纤维细胞 ECM 降解的抑制作用。总之，我们的研究结果表明，Nampt 在 SUI 中过表达，而沉默 Nampt 增强了 SUI 成纤维细胞自噬，从而抑制了 ECM 降解。
